PRINCIPLE: Platform Randomised Trial of Treatments in the Community for Epidemic and Pandemic Illnesses
University of Oxford · Academic
Expired The latest version ended on 24 March 2023. The September 2026 register still lists the agreement, but its term has passed.
- Reference
- DARS-NIC-411161-G4K7X
- Latest version
- v5.4
- Term of latest version
- 25 March 2022 to 24 March 2023
- Start date
- 5 November 2020
- Data controller
- Sole Data Controller
- Commercial purposes
- No
- Sublicensing
- No
- Files released to date
- 110
Why the data was released
Objective for processing
Currently, there are no treatments that have been proven in rigorous trials to help people with COVID-19 symptoms in the community recover quicker and reduce the need for hospital admission. It is therefore vital that the University of Oxford use this opportunity to accelerate enrolment into COVID-19 therapeutics trials.
The PRINCIPLE (Platform Randomised Trial of Treatments in the Community for Epidemic and Pandemic Illnesses) trial is the only national Urgent Public Health priority clinical trial evaluating potential therapeutics for COVID-19 in the primary care setting, endorsed by the Chief Medical Offers (CMOs) of all four devolved nations. The trial aims to find out whether early treatment in the community speeds recovery and reduces the need for hospital admission for those with COVID-19 Illness.
PRINICIPLE is:
• Recruiting across the whole UK*: anyone aged 18 or over can participate, regardless of location.
• Light burden for both recruiters and patients; it only takes couple of minutes to complete enrolment on to the trial.
• Obtaining consent, checking eligibility, issuing study medication and materials, and follow-up is managed remotely through a central facility.
*PLEASE NOTE - The University of Oxford is obtaining data under this agreement from NHS Digital related to residents in England only.
Primary objective - To assess effectiveness of trial treatments in reducing the need for hospital admission or death, for patients aged ≥18 years with confirmed COVID-19 infection during time of prevalent COVID-19 infections.
Secondary objectives - To explore whether trial treatment reduces
1) Participant reported illness severity
2) Duration of severe symptoms
3) Contacts with the health services
4) Consumption of antibiotics
5) Hospital assessment without admission
6) Oxygen administration
7) Intensive Care Unit admission
8) Mechanical ventilation
9) Duration of hospital admission
10) Negative effects on well being
11) New infections in household
12) To investigate the safety of treatments that are not licenced in the UK
The trial was initially only recruiting via GP practices and the website and had c. 1000 participants when use of the Pillar 2 data was first proposed in in order to rapidly increase this to 3,000 (and beyond to support further trial arms). At the time of the second amendment for 28 day follow up data (while also continuing receiving Pillar 2 data) just under 4,500 patients had been recruited. A positive PCR test is required to participate in this trial. The positive PCR test result will be participant reported prior to randomisation, and confirmation of the positive result will be sought at a later date via the Pillar 2 dataset. A positive lateral flow test in a symptomatic person qualifies for randomisation and inclusion in the main analysis will be dependent on the positive PCR test.
The University of Oxford would like to receive names and contact details (including preferably a telephone number and email address) of people who have received a positive COVID-19 swab result from the Pillar 2 testing system. The trial team based in Oxford will then contact these potential participants, inform them about the trial and if they are willing, go on to screen and obtain consent for them to participate in the PRINCIPLE trial. Daily, the trial team would like to receive data on a random cohort (initially 200, now up to 500) of people aged 18 years or over. This number is based on the capacity of the trial team to make the phone calls on a daily basis, and also the relatively low conversion rate of patients contacted that go on to be randomised into the trial (ranging from 1-5% of total number of patients contacted).
Consideration was originally given to whether the trial should be contacting individuals directly, and whether the recruitment could be managed through the Test and Trace service, i.e. the service are already set up to contact individuals and could inform them of the trial when they get in touch. However, given the use of contractors to operate this service, and thereby creating an extra layer to the process, it was unlikely to fit with the timescales the trial were working to (which tied in with why they decided to switch from GPs as the primary source of recruitment). Additionally, the trial already had a centre set up and operating remotely to manage this recruitment in a timely manner.
The question of whether ‘cold calling’ is appropriate has been considered for this application, as time is of the essence for recruitment into PRINCIPLE, telephone is the most efficient and quickest means to ensure direct contact with the individual, who can answer questions instantly over a call. This also ensures ‘human contact’, with trained and experienced CTU research nurses working directly to the trial team providing that contact. The study team would also like to use the Short Messaging Service (SMS) and email option for invitation for those patients who cannot be reached via telephone or those who require a follow-up information. During the calls, clear explanation will be given to individual about how the trial has been able to contact them and what to do if they do not wish to be contacted again (i.e. registering a national opt-out). The trial team will apply the Telephone Preference Service. Recruitment to the trial will be undertaken by substantive employees of the University of Oxford who have been appropriately trained in data protection and confidentiality. Lessons have been learned from a recent NHS Digital request for contact details provided to researchers contact people to donate blood and plasma, with careful attention paid to the various take up rates and any changes rates in these between the first and second waves of the pandemic. However, unlike that trial, PRINCIPLE could potentially be of direct benefit to the individual.
Other considerations that have been taken into account in relation to contacting individuals:
• The data relating to positive COVID-19 tests is sent to NHS Digital at the same time that it is sent to the Business Services Authority, the latter process triggering the SMS to the individual informing them of their result. It then takes around four hours for the Covid-19 UK Non-hospital Antigen Testing Results (Pillar 2) dataset within NHS Digital to be updated with this information. Given that this information then needs to be extracted from the dataset at some point in the next 24 hours, then used by the trial team to make contact with the individual, the risk of the individual being informed of their test result by the trial team before they have read their SMS is small. However, the trial team should have a suitable script prepared to deal with this slim possibility.
• The chances of people having multiple positive COVID-19 test results are rare, and rarer still is the likelihood that they will be one of the 500 people extracted from the thousands of daily test results to be sent to the trial team on more than one occasion. Therefore the risk of an individual being contacted twice for recruitment into PRINCIPLE is extremely low.
• NHS Digital recognises that there are likely to be more requests of this nature in future and therefore, if multiple trial require extracts of people to contact, suitable controls need to be in place within the extract process to ensure that individuals are not getting contacted for recruitment into trials more than is reasonably expected.
*********************** VERSION 5 - MARCH 2022 - STUDY TEAM STATEMENT:
The study team at the University of Oxford are aware the recent governmental change in policy over CV-19 testing that will have a significant impact upon the way testing records will be collected. and how the results should be interpreted. Therefore, the study team will inevitably have to actively incorporate this measure in their study design, which will be reflected in future versions of the study Protocol, processing methodology and outcome analyses.
************************
PATIENT AND PUBLIC INVOLVEMENT & ENGAGEMENT (PPIE)
The PRINCIPLE trial has had PPIE engagement to support development of trial materials and processes and to discuss the plans for efficient and safe use of patient data. The following are further examples of PPIE:
Feedback on the use of data to contact people with a COVID-19 positive test and invite them to
take part in PRINCIPLE:
As part of the NHS Digital Agreement, PRINCIPLE has access to a daily list of potentially recruits who have tested positive for COVID-19 within 24-48 hours from Test and Trace. A survey, developed to understand public perceptions of this approach, was shared with 92 members of patient and public panels and networks linked to Health Data Research UK. 97% of respondents believed this would be an ethical use of data and 68% felt that they would be comfortable or very comfortable with their test result and contact information being provided to researchers for this purpose.
Feedback from PRINCIPLE participants on the study design:
A UK-wide survey of recruited participants to the PRINCIPLE trial found that, of 291 participants, 90%
said the information received before taking part prepared them for their experience on the study, 94% said research staff had always treated them with courtesy and respect and 96% said they would take part in research again.
SUMMARY CARE RECORD DATA:
• Request to use SCR for consented participants:
Supplementary to the requirement to receive Pillar 2 data for recruitment into PRINCIPLE, the trial team have requested access to the Summary Care Record (SCR) for all patients recruited into the trial for the purposes of ensuring timely prescribing and safe patient care.
Previously, up to 40% of people who provided consent to participate in the PRINCIPLE Trial were delayed in starting their trial medication, or were effectively denied the opportunity to participate because of delays in checking information concerning their eligibility to safely be given the study treatments. Because so many people who are keen to contribute are being lost to the PRINCIPLE Trial, crucial study results were not attainable. If processes around ensuring timely, safe prescribing and patient care could be enhanced, then time to potentially life-saving trial results will be reduced.
Version 4 of this agreement sought, and gained permission for the clinical trial team, a group of dedicated doctors and nurses who are fully qualified, study-trained, accredited and registered, to review consenting patients’ Summary Care Records (SCR), in order to be able to confirm key information obtained from the patient relevant to safe patient care in the trial. Only nurses and doctors who are registered and accredited with the General Medical Council of the UK or the Nursing and Midwifery Council of the UK who are clinical members of the PRINCIPLE Study team would review the Summary Care Record for information relevant to safe prescribing and participant care.
The Summary Care Record is used as a timely, second check regarding medication, allergy, and co-morbidities information to support reconciliation, to ensure safe prescribing. These are all elements of a patient’s SCR with additional information which is a subset of their wider GP record. This access provides an immediate available information source to meet the need to support safe prescribing in a proportionate and timely way. In addition, the Summary Care Record provides a further safety check, in that access to it facilitates the opportunity for double-checking participants’ NHS Number and GP practice.
Previously, PRINCIPLE Trial procedures involved the clinical trial team endeavouring to identify a consenting patient’s GP, emailing or posting the participant’s consent form to the GP to obtain relevant clinical information for the study clinical team to confirm eligibility, then waiting for the GP to send selected summary clinical information from the patient’s record back to the trial clinical team, before it is then checked against patient-reported information. This proportionate access also minimises the burden on frontline general practice at a time of considerable pressures.
Access is only for those potential participants who have screened eligible to be part of the Trial, and who have already signed informed consent for participation in the study and for the Trial to access their clinical records. All potential participants are asked specifically for permission for the trial team to access their medical records and have the opportunity to decline this access. In addition, they are being asked specifically and separately for permission about access to their Summary Care Record. For a patient who has provided consent to join the trial and for their SCR to be accessed, the data will be accessed by a clinician to support safe prescribing decisions immediately prior to prescribing medications. A Summary Care Record will only ever be accessed on one occasion for each individual participant.
Access is required for the period that the trial is recruiting - currently this is April 2020 until March 2023.
• Access in relation the purposes of direct care:
The purpose of SCR is to allow healthcare professionals to check relevant facts prior to carrying out direct care of an individual. The clinical trial will support direct care in this use case as healthcare professionals are carrying out direct care (avoiding dangerous prescribing) for individuals, with the patient’s consent.
There will be no re-use of the data shared for direct care purposes for non-direct care purposes, but the wider context for the use of the data is as part of a clinical trial.
This request for SCR access for PRINCIPLE, along with the similar request for the sister trial, PANORAMIC, together formed a first of type access request and as an interim position it was included in the Data Sharing Agreement. This continues to be a holding position whilst considerations are undertaken to agree whether to offer this as a service more widely to clinical trials for patient safety purposes. This allows time for an appropriate access and approval process to be developed in future, but in the meantime ensures that SCR access is recognised within the research data access process alongside the normal direct care process for access to SCR.
FOLLOW UP DATA:
• Request to receive 28 day follow up data for:
> Hospital Episode Statistics (HES) Admitted Patient Care (APC)
> HES Critical Care (CC)
> Civil Registration (Deaths) data set
> GP Data for Pandemic Planning and Research (GDPPR)
***New request for version 5 of this agreement***
> Medicines dispensed in Primary Care (from the NHS Business Services Authority (NHSBSA) data)
The trial follows up all consented participants for 28 days. For the just over 9,700 participants currently recruited, data for 2,000 of the participants comes from the Royal College of General Practitioners (RCGP) Research and Surveillance Centre platform, but not all GPs are registered with this system. The trial team is currently contacting GPs to collect follow up data for the remaining participants, which is a huge burden on team resource and a slow process.
Due to the high rate of recruitment, the Data Safety Committee review the trial data weekly and can ask for recruitment into a trial arm to be stopped immediately. Therefore trial data needs to be made available as soon as possible so that the team can quickly issue a press statement and publication of results if required to do so. To date, there have been three trial arms stopped, essentially because all required data has not been available immediately and it has taken the team too long to collect that data and issue the information publicly. There is therefore a need to capture the required data in a more timely and efficient manner via monthly extracts from NHS Digital.
Data required is as follows:
- Did the participant attend a hospital for medical reasons between the date of randomisation and day 28 of their follow-up?
- What date did they go to hospital?
- Was this attendance likely related to COVID-19?
- If the hospital attendance was unlikely to be related to COVID-19, what was the reason for the hospital visit?
- Was the hospital attendance to visit A&E?
- Did they receive oxygen while in hospital?
- Did they receive mechanical ventilation while in hospital?
- Were they admitted overnight?
- If yes, how many nights did they stay in hospital?
- Is the participant still in hospital with this admission?
- Did they stay in an Intensive Care Unit during their stay in hospital?
(The above is to be sourced from the HES APC and Critical Care data).
- Was the participant taking antibiotics for an acute condition when they were randomised to PRINCIPLE?
- If yes, what was the name of the antibiotic?
- Was the participant prescribed any antibiotics between the date of randomisation and day 28 of their follow-up (exclude any antibiotics that may have been given as part of the study intervention)?
- If yes, what was the name of the antibiotic?
- What was the reason for the antibiotic prescription?
- What was the start date of antibiotic course?
- Has the participant been prescribed inhaled medication containing corticosteroids in the past 6 months? (Exclude any inhaled corticosteroids that may have been given as part of the study intervention).
- What date was the participant last prescribed inhaled medication containing corticosteroids before they were randomised?
- Has the participant been in contact with their GP after randomisation and up to an including day 28 of their follow-up?
- If yes, how many times?
(The above is to be sourced from the GDPPR/***Medicines dispensed in Primary Care data (NHSBSA data) ***).
- Has the participant died?
- If yes, what was the date of death?
- What was the cause of death?
- Did COVID-19 contribute to death?
(The above is to be sourced from the Civil Registration of Deaths data).
Consent is in place to allow this data to be provided to the team from NHS Digital and is contained on the latest version of Patient Information Sheet on the trial website (https://www.principletrial.org/participants/participant-information-sheets):
“In addition, we will collect information from your GP records and data held by central NHS bodies (such as NHS Digital) for long-term follow-up for up to 10 years, to help us better understand the long-term effects of COVID-19 and the trial treatments.”
This consent will allow for the analysis of the longer term effects and symptoms on participants in the trial, by comparison of patients on usual care compared to those who received a PRINCIPLE trial treatment/intervention.
Only the team at the University of Oxford will access this data. No other organisations are involved in the processing or storage.
**********
New Request for version 5 of this agreement:
***Request to add Medicines dispensed in Primary Care (NHSBSA data) dataset to the existing 28 day follow up data***:
This additional dataflow will support those already received to follow up consented patients for 28 days. Key secondary outcomes will be obtained from this data output i.e. consumption of antibiotics, which is required for the final analysis of each treatment arm used on the trial. Furthermore, resources such as staff and expense required for the manual process of collecting participant medical notes and reviews from GP practices is very costly, and having access to this data from NHS Digital would reduce the number of working hours previously needed to collect the data. The use of the Medicines dispensed in Primary Care (NHSBSA data) is in line with the direction which is to provide intelligence about the safety and effectiveness of medicines.
The NHSBSA data does encompass similarities to the GDPPR dataset already received as part of this agreement, however the NHSBSA provides extra information on the treatment prescribed beyond antibiotic, such as inhaled corticosteroid. Likewise, the medication data held within the GDPPR dataset provides information that can verify the data from medical notes review, therefore the study team have requested both the NHSBSA and GDPPR datasets for this agreement. The fields chosen within each dataset have been limited ensure that duplication of data is minimised.
As per the previous amendment for 28 follow up data, the existing consent covers the provision of this extra data and it will only be accessed by the team at University of Oxford, and no other organisations will process or store it.
LEGAL BASIS
The lawful basis for the release and use of the confidential data for Covid-19 UK Non-hospital Antigen Testing Results (pillar 2) being shared under this version of the agreement is Regulation 3(4) of the National Health Service (Control of Patient Information Regulations) 2002 (COPI) to require NHS Digital to share confidential patient information with organisations entitled to process this under COPI for COVID-19 purposes. The only permitted activities under this Data Sharing Agreement (DSA) are for COVID-19 purposes and within bounds of Reg 3(2) COPI. Reg 3 (2) COPI states that: "2) For the purposes of this regulation, “processing” includes any operations, or set of operations set out in regulation 2(2) which are undertaken for the purposes set out in paragraph (1)." The research relates to the monitoring and managing of COVID-19 and would therefore be covered by Reg 3(1)(d) of COPI.
NOTE: University of Oxford must rely on the COPI notice for the statutory sharing of information by NHS Digital for COVID-19 purposes. When the COPI notice expires, full support and approval for section 251 from the Confidentiality Advisory Group has been received and will supersede the COPI notice for the release and use of the confidential data (Covid-19 UK Non-hospital Antigen Testing Results (pillar 2) under this agreement.
Consent is in place to allow the access to Summary Care Record (SCR) data and dissemination of pseudonymised follow-up data to be provided to the study team from NHS Digital. Details of the trial and expected data flows are explained on the latest version of Patient Information Sheet which will be hosted on the trial website: https://www.principletrial.org/
Only the study team at the University of Oxford will access the requested NHS Digital record-level data. No other organisations are involved in the processing or storage of NHS Digital record level data. NHS Digital record level data will not leave the UK.
LEGAL BASIS FOR PROCESSING DATA
The University of Oxford, as the Data Controller who is also processing the data will process Personal data under GDPR Article 6 (1) (e) - Processing is necessary for the performance of a task carried out in the public interest or in the exercise of official authority vested in the controller. As a higher education establishment, the University conduct research to improve health care and service and the data requested is necessary for the performance of a task carried out in the public interest.
The trial is of national and international relevance during this pandemic. The primary focus of the trial is treatment of confirmed (PCR positive) SARS-CoV2 infections to speed up recovery, prevent hospitalisation and/or death and reduce symptoms, thus reducing clinical impact of the virus on individuals and the strain on NHS hospitals, thus research very much in the public interest.
Additionally, under GDPR Article 9(2)(j) processing of Special Category Personal Data (of which Health data is one) is necessary for archiving for research purposes. Data minimisation process is being followed and only data that is required specifically for the purposes of this study has been requested, to protect the rights of the data subjects. The data are required for research purposes in the public interest – meeting the conditions in the DPA 2018 Schedule 1 Part 1 (4) – which GDPR Recital 52(2) determines is an appropriate derogation from the prohibition on processing special categories of personal data.
Article 9(2)(h) is additionally being used to cover the processing of SCR specifically: ‘processing is necessary for the purposes of preventive or occupational medicine, for the assessment of the working capacity of the employee, medical diagnosis, the provision of health or social care or treatment or the management of health or social care systems and services’ as it is being used as a timely, second check regarding medication, allergy, and co-morbidities information to support reconciliation, to ensure safe prescribing.
In accordance with GDPR Article 89(1) processing is subject to appropriate safeguards. These include:
- The data recipient’s technical and organisational measures to safeguard the data have been assessed and meet NHS Digital’s acceptance criteria (see sections 2 and 5b of this application for further details;
- The requested data has been assessed as proportionate to the aim pursued (see section 5a of this application for further details);
Controls, data retention and processing activities have been assessed to ensure respect to the essence of the right to data protection (see sections 5a, 5b and 8a of this application for further details);
- Measures to protect the rights and freedoms of data subjects have been assessed including transparency (fair processing) publishing subject’s rights to withdraw consent and /or have their data erased or rectified, etc.
The PRINCIPLE trial is funded by the National Institute of Health Research (NIHR) and UK Research and Innovation (UKRI) Medical Research Group (MRC). NIHR and UKRI MRC do not make any decisions determining the purposes and means of the processing of data or the study purpose and methodology, and are therefore not considered as Data Controllers. Additionally, the NIHR and UKRI MRC will not have access to any NHS Digital record level data and are therefore not considered as Data Processors.
A collaborator agreement is in place between University of Oxford and the institutions listed on the protocol for this clinical trial. The study team have confirmed that the institutions listed within the protocol will not have access to NHS Digital record level data and therefore, in line with NHS Digital’s DARS standards, does not consider these other institutions as joint Data Controllers or Data Processors for this agreement.
Processing activities
The trial is run remotely, therefore removing the need for participants to be near to a GP practice. Screening and contact with the trial team is all done online. The study team have requested access to the participants summary care record, to ensure safe prescribing – for example, that they will not be allergic to the proposed treatments. The trial team may however contact the participant’s GP should any concerns arise regarding uncertainties with the information provided within the participants Summary Care Record, or should the participant not consent for access to the SCR. The Patient Information Sheet states:
“We will ask for your consent to view your SCR. The SCR will not be retained by the trial team. If your SCR is unavailable or you do not consent for us to access it, you can still take part in the trial as we will obtain this information from your GP.”
Covid-19 UK Non-hospital Antigen Testing Results (pillar 2) - The processing of the data will be as follows:
• On a daily basis (seven days a week) NHS Digital will interrogate the Pillar 2 dataset and extract up to 500 individuals at random who are aged 18 or over who have received a positive COVID-19 test result in the previous 24 hours.
• The individuals will be residents of England-only.
• Filters will be applied to remove patients who have registered a National Data Opt-Out, as well as special categories of people for whom the data should not be disseminated. The purpose of the restriction is to ensure that patient information that might imply a location is protected.
• Individuals who have signed up for the Telephone Preference Service will not be contacted via telephone.
• The flow from NHS Digital to University of Oxford will be automated via a Secure Electronic File Transfer service (SEFT.)
• University of Oxford will use the data provided to make outbound communications to ask if eligible individuals would be interested in being recruited into the trial.
• The aim is to recruit 100 people into the trial per day.
• The number of individual contact details supplied by NHS Digital to University of Oxford will be reviewed once the take-up rate is better understood.
The trial team in Oxford will hold the data securely adhering to all Information Governance (IG) Policies in the department. The trial team will call these contacts to inform them of the trial, screen, consent and randomise them.
The identifiable data received from NHS Digital will be deleted on a weekly basis as the trial team will no longer require it.
Statistical data analysis will be carried out via University of Oxford owned devices connected to the University of Oxford network either directly in person or remotely, using an appropriate statistical package. To remotely access the devices requires a secure 2-factor authenticator (VPN) and users are then able to securely access the secure server on the University’s IT framework. All data analysis will be conducted within the confines of the University’s secure server, and will not be downloaded to remote devices for storage or processing.
Berry Consultancy in the USA will also be undertaking data analysis, however this will be performed using non-NHS Digital data. No NHS Digital record-level data will be processed by any organisation not already stated in this agreement, nor will any NHS Digital record-level data be sent, stored or processed outside of the UK.
• Request to use Summary Care Record (SCR) for consented participants:
Once participants are recruited into PRINCIPLE, the trial team will access their Summary Care Record. This will be through ‘SCR Core’ or ‘SCR Additional Information’, depending on what is available for each participant.
SCR Core includes:
• current medication
• allergies and details of any previous bad reactions to medicines
• the name, address, date of birth and NHS number of the patient
SCR Addition Information includes:
• significant medical history (past and present)
• reason for medication
• anticipatory care information (such as information about the management of long term conditions)
• end of life care information (from the SCCI1580 national dataset)
• immunisations.
Data is minimised as access is only for the consented cohort for the trial.
The Clinical trial team will use SCR and build on best practice by identifying the patient’s NHS number after a demographic search and using this to confirm the patient’s identity as well as ensuring the NHS Number is noted on any paperwork being returned to the patient’s practice regarding their participation in the trial.
The SCR Team at NHS Digital will create a new position for the trial team which allows access to SCR via SCRa/Spine Portal and does not include emergency access. SCR access is time limited for the duration of the trial; this will be achieved with the use of roles to be applied to smartcards to be time limited for the duration of the trial.
The trial team will not retain information obtained from SCR once the eligibility checks have been done: they will record that the SCR has been accessed, and the audit trail within the SCR will also log who has accessed the record.
• Request to receive 28 day follow up data (HES APC, HES Critical Care, GDPPR, ***Medicines dispensed in Primary Care data*** and Civil Registration of Deaths):
On a monthly basis the trial team will send to NHS Digital the relevant data items for those cohort members who have hit the 28 day follow up window.
The University of Oxford will provide NHS Digital with the following information via Secure Electronic File Transfer (SEFT) for consented participants:
• Study ID
• NHS Number
• Date of Birth
• Trial recruitment date
• withdrawal date (if applicable)
NHS Digital will link the cohort members to the aforementioned datasets and return the record-level pseudonymised outputs to the Study team at the University of Oxford via SEFT.
NHS Digital Record Level Data will not be linked to any other datasets.
One of the data sets requested in this agreement (GPES Data for Pandemic Planning and Research - GDPPR) has been collected under a specific COVID-19 related direction, and as such can only be used for COVID-19 research related purposes. The COPI notice that will cover this flow of data is currently set to expire on 30 June 2022.
**********
New Request for version 5 of this agreement:
*** Request to add Medicines dispensed in Primary Care (NHSBSA data) dataset to the existing 28 day follow up data***
• In addition to the previous request for 28 day follow up data, data from the Medicines dispensed in Primary Care (NHSBSA data) dataset will be linked to the cohort and provided to University of Oxford on a monthly basis and in line with the existing transfer and security arrangements.
HES and ECDS DISCLOSURE CONTROL / SMALL NUMBER SUPPRESSION
In order to protect patient confidentiality, when presenting results calculated from HES record level data, outputs will contain only aggregate level data with small numbers suppressed in line with HES Analysis Guide. When publishing HES data, data processors must make sure that:
• National-level figures only may be presented unrounded, without small number suppression
• cell values from 1 to 7 (inclusive) are suppressed at a sub-national level to prevent possible identification of individuals from small counts within the table.
• Zeros (0) do not need to be suppressed.
• All other counts will be rounded to the nearest 5.
Data will not be made available to any third parties other than those specified except in the form of aggregated outputs with small numbers suppressed in line with the HES Analysis Guide.
Expected output
All outputs will be aggregated with small number suppression applied as per the HES analysis guide.
The PRINCIPLE trial should be able to recruit to target much quicker than using current methods if the team can receive the requested NHS Digital identifiable data. The statistical team will aim to receive follow up data in a more timely manner, therefore answering the COVID-19 treatment in the community question more quickly with the aim of preventing covid-19 patients being hospitalised so in turn reducing NHS burden.
It appears to take between 800-1200 patients per arm to answer the question for the drug of that arm. 1500 per arm is the target recruitment number, and just over 9,700 patients have been recruited at the time of the fifth amendment to this agreement. Five arms have been closed so far, leaving two arms open, with potential for more arms to follow thereafter.
The trial team intends to disseminate results via media channels: pre-prints/publications in peer-reviewed journals such as The Lancet, press releases in local and national newspapers; BBC news coverage; Department of Health and Social Care (DHSC) press briefings; DHSC Social media updates; Twitter and Facebook University of Oxford accounts. The study team intend to disseminate results to trial participants via the trial website, supported by the University of Oxford. The study team plan to provide regular updates to the NIHR Evaluation, Trials and Studies Coordinating Centre.
The study team intend to update participants by signposting them from their ‘end of trial letter’ to the trial website for the latest results and information. Due to the limited resources of the study trial team and the potential number of study participants involved, the study trial team have made the decision that distributing newsletters or email updates would be difficult to manage at such a scale. The study trial team believe that signposting to the website also ensures that the most up to date information is always available to participants, as newsletters can soon become outdated due to the fast-paced and evolving nature of this platform trial. The study team are also considering the use of video/audio updates and other formats to the website depending on capacity.
The trial is of national and international relevance during this pandemic.
Expected measurable benefits
COVID-19 treatments in the community, if deployed rapidly, have the potential to prevent transmission, reduce symptoms and hospitalisations, all of which hope to protect the vital gains of the vaccination programme, particularly if new variants of concern emerge which reduce vaccine efficacy. The emergence of the SARS-CoV2 virus has had a profound impact on the UK population. It is vital to ensure that a significant rise in infections and spread of the virus in the population is controlled as far as possible. The identification of treatments is integral to a longer-term response to COVID-19 and should enhance pandemic preparedness in the years ahead.
The primary focus of the trial is treatment of confirmed (PCR positive) SARS-CoV2 infections to speed up recovery, prevent hospitalisation and/or death and reduce symptoms, thus reducing clinical impact of the virus on individuals and the strain on NHS hospitals.
Original target date was to recruit 3,000 participants by December 2020. The study team now have a new target to continue recruiting beyond the 9,700 patients already recruited.
Benefits reported so far
PRINCIPLE is the world’s largest Phase 3 platform randomised controlled trial of possible COVID-19 treatments for recovery at home. The trial has evolved to represent the first ‘democratic', nationally inclusive trial of an acute condition in the UK, through the use of online consent, remote eligibility checking, remote randomisation, online/telephone follow-up and central distribution of study materials direct to the participant. PRINCIPLE has proven ability to suspend and add treatment arms while the study is in progress, investigating seven potential COVID-19 treatments in 18 months, recruiting more than 9,700 participants . PRINCIPLE has successfully identified budesonide as the first previously licensed, inexpensive COVID-19 treatment, which the Chief Medical Officer has recommended on a case-by-case basis. The results have also shown that azithromycin and doxycycline are not generally effective treatments for COVID-19. The UK-wide opportunity to contribute to this research has been a major transformative achievement for the trial. PRINCIPLE is especially committed to reaching disadvantaged populations, typically under-researched, with a trial National Pharmacy and Ethnic Minority Communities Research Lead. It has achieved comparable representations for ethnic minority and socioeconomically deprived participants to national figures for its target population.
PRINCIPLE was recognised by the ‘Health Data Research UK (HDR UK) Impact of the Year Award 2021’ as a leading example of the innovative use of primary care data whilst working at pace and scale. The trial has successfully co-ordinated data flows from over 3100 GP sites (including Notes Review Case Report Forms (CRF) completed by GPs at trial sites), combined with routinely collected electronic NHS data through partnership with the NHS Digital Information Governance Team, the Information Commissioner’s Office, NHS Test & Trace, NHS DigiTrials Health Data Research (HDR) Hub, the Department of Health and Social Care (DHSC), and the HDR UK Public & Patient Involvement and Engagement Team, to obtain data as close to real-time as possible, with primary outcome data available for 95% of participants.
Datasets on the latest version
Legal basis for provision: CV19: Regulation 3 (4) of the Health Service (Control of Patient Information) Regulations 2002; Health and Social Care Act 2012 - s261 - 'Other dissemination of information'; CV19: Regulation 3 (4) of the Health Service (Control of Patient Information) Regulations 2002; Health and Social Care Act 2012 – s261(2)(c); CV19: Regulation 3 (4) of the Health Service (Control of Patient Information) Regulations 2002; Health and Social Care Act 2012 – s261(7); National Health Service Act 2006 - s251 - 'Control of patient information'.
| Dataset | Type of data | Sensitivity | Frequency | Confidential data |
|---|---|---|---|---|
| Civil Registrations of Death | Anonymised - ICO Code Compliant | Sensitive | Ongoing | Statutory exemption to flow confidential data without consent |
| COVID-19 Access to Summary Care Records | Identifiable | Sensitive | System Access | Statutory exemption to flow confidential data without consent |
| COVID-19 General Practice Extraction Service (GPES) Data for Pandemic Planning and Research (GDPPR) | Identifiable | Sensitive | Ongoing | Statutory exemption to flow confidential data without consent |
| COVID-19 UK Non-hospital Antigen Testing Results (Pillar 2) | Identifiable | Sensitive | One-Off | Statutory exemption to flow confidential data without consent |
| Hospital Episode Statistics Admitted Patient Care (HES APC) | Anonymised - ICO Code Compliant | Non-Sensitive | Ongoing | Statutory exemption to flow confidential data without consent |
| Hospital Episode Statistics Critical Care (HES Critical Care) | Anonymised - ICO Code Compliant | Non-Sensitive | Ongoing | Statutory exemption to flow confidential data without consent |
| Medicines dispensed in Primary Care (NHSBSA data) | Anonymised - ICO Code Compliant | Non-Sensitive | Ongoing | Statutory exemption to flow confidential data without consent |
Files released
Files released counts only files released externally by DARS. Access granted in NHS England's own systems, such as its Secure Data Environment, is not included.
Patient opt-outs were applied to 37 of the 110 files released under this agreement, across every version. About opt-outs
Files released against version 5.4 of this agreement, summarised by dataset.
| Dataset | Files | First released | Last released | Opt-outs applied |
|---|---|---|---|---|
| Civil Registrations of Death | 10 | April 2022 | January 2023 | Mixed |
| Hospital Episode Statistics Admitted Patient Care (HES APC) | 5 | April 2022 | September 2022 | No |
| Hospital Episode Statistics Critical Care (HES Critical Care) | 3 | April 2022 | September 2022 | No |
| COVID-19 General Practice Extraction Service (GPES) Data for Pandemic Planning and Research (GDPPR) | 1 | April 2022 | April 2022 | No |
Version history
The register lists each renewal of this agreement as a separate row. This site has 6 versions.
DARS-NIC-411161-G4K7X-v5.4 25 March 2022 to 24 March 2023
- Title
- PRINCIPLE: Platform Randomised Trial of Treatments in the Community for Epidemic and Pandemic Illnesses
- Commercial
- No
- Sublicensing
- No
- Datasets
- 7
- Files released
- 19
Datasets: Civil Registrations of Death; COVID-19 Access to Summary Care Records; COVID-19 General Practice Extraction Service (GPES) Data for Pandemic Planning and Research (GDPPR); COVID-19 UK Non-hospital Antigen Testing Results (Pillar 2); Hospital Episode Statistics Admitted Patient Care (HES APC); Hospital Episode Statistics Critical Care (HES Critical Care); Medicines dispensed in Primary Care (NHSBSA data)
What changed from DARS-NIC-411161-G4K7X-v4.4
Text removed is struck through; text added is underlined. Unchanged paragraphs are summarised rather than repeated.
| Field | Was | Became |
|---|---|---|
| Title | PRINCIPLE: Platform Randomised Trial of Treatments in the Community for Epidemic and Pandemic Illnesses | |
| Start date | 2022-03-25 | |
| End date | 2023-03-24 | |
| COVID-19 Access to Summary Care Records: legal basis | CV19: Regulation 3 (4) of the Health Service (Control of Patient Information) Regulations 2002; Health and Social Care Act 2012 – s261(2)(c) | |
| COVID-19 General Practice Extraction Service (GPES) Data for Pandemic Planning and Research (GDPPR): legal basis | CV19: Regulation 3 (4) of the Health Service (Control of Patient Information) Regulations 2002; Health and Social Care Act 2012 – s261(2)(c) | |
| COVID-19 UK Non-hospital Antigen Testing Results (Pillar 2): legal basis | CV19: Regulation 3 (4) of the Health Service (Control of Patient Information) Regulations 2002; Health and Social Care Act 2012 – s261(7); National Health Service Act 2006 - s251 - 'Control of patient information'. | |
| Civil Registrations of Death: legal basis | CV19: Regulation 3 (4) of the Health Service (Control of Patient Information) Regulations 2002; Health and Social Care Act 2012 - s261 - 'Other dissemination of information' | |
| Hospital Episode Statistics Admitted Patient Care (HES APC): legal basis | CV19: Regulation 3 (4) of the Health Service (Control of Patient Information) Regulations 2002; Health and Social Care Act 2012 - s261 - 'Other dissemination of information' | |
| Hospital Episode Statistics Critical Care (HES Critical Care): legal basis | CV19: Regulation 3 (4) of the Health Service (Control of Patient Information) Regulations 2002; Health and Social Care Act 2012 - s261 - 'Other dissemination of information' |
Datasets: + Medicines dispensed in Primary Care (NHSBSA data)
Objective for processing
Over recent weeks, there has been an increase in the number of COVID-19 cases in the community and in hospitalisation.
Currently, there are no treatments that have been proven in rigorous trials
[25 words unchanged]
of Oxford use this opportunity to accelerate enrolment into COVID-19 therapeutics trials.
The PRINCIPLE (Platform Randomised
trial
Trial
of
Interventions against COVID-19 In older peoPLE)
Treatments in the Community for Epidemic and Pandemic Illnesses)
trial is the only national Urgent Public Health priority clinical trial evaluating potential therapeutics for COVID-19 in the primary care setting, endorsed by the
CMOs
Chief Medical Offers (CMOs)
of all four devolved
nations .
nations.
The trial aims to find out whether early treatment in the community speeds recovery and reduces the need for hospital admission for those with
COVID-like-Illness.
COVID-19 Illness.
[1 paragraph unchanged]
• Recruiting across the whole
UK:
UK*:
anyone
aged 18 or over
can participate, regardless of location.
[1 paragraph unchanged]
• Obtaining consent, checking eligibility, issuing study medication and materials, and follow-up is
manged
managed
remotely through a central facility.
Primary objective - To assess effectiveness of trial treatments in reducing the need for hospital admission or death, for patients aged ≥50 years with comorbidity, and aged ≥65 with or without comorbidity and suspected COVID-19 infection during time of prevalent COVID-19 infections.
*PLEASE NOTE - The University of Oxford is obtaining data under this agreement from NHS Digital related to residents in England only.
Primary objective - To assess effectiveness of trial treatments in reducing the need for hospital admission or death, for patients aged ≥18 years with confirmed COVID-19 infection during time of prevalent COVID-19 infections.
[1 paragraph unchanged]
1) Duration of severe symptoms
1) Participant reported illness severity
2) Time taken to self-report recovery
2) Duration of severe symptoms
[6 paragraphs unchanged]
9) To determine if effects are specific to those with the infections syndrome but who test positive for COVID-19
9) Duration of hospital admission
10) Duration of hospital admission
10) Negative effects on well being
The trial was initially only recruiting via GP practices and the website and had c. 1000 participants when use of the Pillar 2 data was first proposed in in order to rapidly increase this to 3,000 (and beyond to support further trial arms). At the time of the second amendment for 28 day follow up data (while also continuing receiving Pillar 2 data) just under 4,5000 patients had been recruited.
11) New infections in household
The University of Oxford would like to receive names and contact details (preferably a telephone number) of people who have received a positive covid-19 swab result from the Pillar 2 testing system. The trial team based in Oxford will then contact these potential participants, inform them about the trial and if they are happy, go on to screen and consent them into Principle. Daily, the trial team would like to receive data on a random cohort (initially 200, now up to 500) of people aged 50+. They may need to increase this age to 65+ if those they contact screen as ineligible for the trial as they lack the required comorbidities.
12) To investigate the safety of treatments that are not licenced in the UK
Consideration has been given to whether the trial should be contacting individuals directly, and whether the recruitment could be managed through the Test and Trace service, i.e. the service are already set up to contact individuals and could inform them of the trial when they get in touch. However, given the use of contractors to operate this service, and thereby creating an extra layer to the process, this is unlikely to fit with the timescales the trial are working to (which ties in with why they have decided to switch from GPs as the primary source of recruitment). Additionally, the trial already has a centre set up and operating remotely to manage this recruitment in a timely manner.
The trial was initially only recruiting via GP practices and the website and had c. 1000 participants when use of the Pillar 2 data was first proposed in in order to rapidly increase this to 3,000 (and beyond to support further trial arms). At the time of the second amendment for 28 day follow up data (while also continuing receiving Pillar 2 data) just under 4,500 patients had been recruited. A positive PCR test is required to participate in this trial. The positive PCR test result will be participant reported prior to randomisation, and confirmation of the positive result will be sought at a later date via the Pillar 2 dataset. A positive lateral flow test in a symptomatic person qualifies for randomisation and inclusion in the main analysis will be dependent on the positive PCR test.
The question of whether ‘cold calling’ is appropriate has been considered for this application, especially against alternatives such as SMS and emailing. As time is of the essence for recruitment into PRINCIPLE, telephone is the most efficient and quickest means to ensure direct contact with the individual, who can answer questions instantly over a call. This also ensures ‘human contact’, as opposed to SMS / emails, with trained and experienced CTU research nurses working directly to the trial team providing that contact. During the calls, clear explanation will be given to individual about how the trial has been able to contact them and what to do if they do not wish to be contacted again (i.e. registering a national opt-out). The trial team will decide whether to apply the Telephone Preference Service under their own discretion. The trial team will also ensure the required comorbidities are discussed early on in the calls so as to not to get the individual’s hopes up if they are not in fact eligible for the trial. Lessons have been learned from a recent NHS Digital request for contact details provided to researchers contact people to donate blood and plasma, with careful attention paid to the various take up rates and any changes rates in these between the first and second waves of the pandemic. However, unlike that trial, PRINCIPLE could potentially be of direct benefit to the individual.
The University of Oxford would like to receive names and contact details (including preferably a telephone number and email address) of people who have received a positive COVID-19 swab result from the Pillar 2 testing system. The trial team based in Oxford will then contact these potential participants, inform them about the trial and if they are willing, go on to screen and obtain consent for them to participate in the PRINCIPLE trial. Daily, the trial team would like to receive data on a random cohort (initially 200, now up to 500) of people aged 18 years or over. This number is based on the capacity of the trial team to make the phone calls on a daily basis, and also the relatively low conversion rate of patients contacted that go on to be randomised into the trial (ranging from 1-5% of total number of patients contacted).
Consideration was originally given to whether the trial should be contacting individuals directly, and whether the recruitment could be managed through the Test and Trace service, i.e. the service are already set up to contact individuals and could inform them of the trial when they get in touch. However, given the use of contractors to operate this service, and thereby creating an extra layer to the process, it was unlikely to fit with the timescales the trial were working to (which tied in with why they decided to switch from GPs as the primary source of recruitment). Additionally, the trial already had a centre set up and operating remotely to manage this recruitment in a timely manner.
The question of whether ‘cold calling’ is appropriate has been considered for this application, as time is of the essence for recruitment into PRINCIPLE, telephone is the most efficient and quickest means to ensure direct contact with the individual, who can answer questions instantly over a call. This also ensures ‘human contact’, with trained and experienced CTU research nurses working directly to the trial team providing that contact. The study team would also like to use the Short Messaging Service (SMS) and email option for invitation for those patients who cannot be reached via telephone or those who require a follow-up information. During the calls, clear explanation will be given to individual about how the trial has been able to contact them and what to do if they do not wish to be contacted again (i.e. registering a national opt-out). The trial team will apply the Telephone Preference Service. Recruitment to the trial will be undertaken by substantive employees of the University of Oxford who have been appropriately trained in data protection and confidentiality. Lessons have been learned from a recent NHS Digital request for contact details provided to researchers contact people to donate blood and plasma, with careful attention paid to the various take up rates and any changes rates in these between the first and second waves of the pandemic. However, unlike that trial, PRINCIPLE could potentially be of direct benefit to the individual.
[1 paragraph unchanged]
• The data relating to positive
COVID19
COVID-19
tests is sent to NHS Digital at the same time that it
[17 words unchanged]
them of their result. It then takes around four hours for the
Pillar 2
Covid-19 UK Non-hospital Antigen Testing Results (Pillar 2)
dataset within NHS Digital to be updated with this information. Given that
[57 words unchanged]
should have a suitable script prepared to deal with this slim possibility.
• The chances of people having multiple positive
COVID19
COVID-19
test results are rare, and rarer still is the likelihood that they
[31 words unchanged]
an individual being contacted twice for recruitment into PRINCIPLE is extremely low.
[1 paragraph unchanged]
********************
*********************** VERSION 5 - MARCH 2022 - STUDY TEAM STATEMENT:
The study team at the University of Oxford are aware the recent governmental change in policy over CV-19 testing that will have a significant impact upon the way testing records will be collected. and how the results should be interpreted. Therefore, the study team will inevitably have to actively incorporate this measure in their study design, which will be reflected in future versions of the study Protocol, processing methodology and outcome analyses.
************************
PATIENT AND PUBLIC INVOLVEMENT & ENGAGEMENT (PPIE)
The PRINCIPLE trial has had PPIE engagement to support development of trial materials and processes and to discuss the plans for efficient and safe use of patient data. The following are further examples of PPIE:
Feedback on the use of data to contact people with a COVID-19 positive test and invite them to
take part in PRINCIPLE:
As part of the NHS Digital Agreement, PRINCIPLE has access to a daily list of potentially recruits who have tested positive for COVID-19 within 24-48 hours from Test and Trace. A survey, developed to understand public perceptions of this approach, was shared with 92 members of patient and public panels and networks linked to Health Data Research UK. 97% of respondents believed this would be an ethical use of data and 68% felt that they would be comfortable or very comfortable with their test result and contact information being provided to researchers for this purpose.
Feedback from PRINCIPLE participants on the study design:
A UK-wide survey of recruited participants to the PRINCIPLE trial found that, of 291 participants, 90%
said the information received before taking part prepared them for their experience on the study, 94% said research staff had always treated them with courtesy and respect and 96% said they would take part in research again.
SUMMARY CARE RECORD DATA:
[1 paragraph unchanged]
Supplementary to the requirement to receive Pillar 2 data for recruitment into PRINCIPLE, the trial team
will
have requested
access
to
the Summary Care Record (SCR)
of
for
all patients recruited into the trial for the purposes of ensuring timely prescribing and safe patient care.
Currently,
Previously,
up to 40% of people who
provide
provided
consent to participate in the PRINCIPLE Trial
are
were
delayed in starting their trial medication, or
are
were
effectively denied the opportunity to participate because of delays in checking information
[17 words unchanged]
to contribute are being lost to the PRINCIPLE Trial, crucial study results
are
were
not
yet forthcoming.
attainable.
If processes around ensuring timely, safe prescribing and patient care could be enhanced, then time to potentially life-saving trial results will be reduced.
The purpose
Version 4
of this
request is therefore to seek
agreement sought, and gained
permission for the clinical trial team, a group of dedicated doctors and nurses who are fully qualified, study-trained, accredited and registered, to review consenting patients’ Summary Care
Records,
Records (SCR),
in order to be able to confirm key information obtained from the patient relevant to safe patient care in the trial. Only nurses and doctors who are
qualified, trained and fully
registered and accredited with the General Medical Council of the UK or
[20 words unchanged]
Summary Care Record for information relevant to safe prescribing and participant care.
The Summary Care Record
will be
is
used as a timely, second check regarding medication, allergy, and co-morbidities information
[43 words unchanged]
in a proportionate and timely way. In addition, the Summary Care Record
will provide
provides
a further safety check, in that access to it
will facilitate
facilitates
the opportunity for double-checking participants’ NHS Number and GP practice.
Current
Previously,
PRINCIPLE Trial procedures
involve
involved
the clinical trial team endeavouring to identify a consenting patient’s GP, emailing
[56 words unchanged]
the burden on frontline general practice at a time of considerable pressures.
Access is
sought
only for those
people
potential participants
who have screened eligible to be part of the Trial, and who
[35 words unchanged]
records and have the opportunity to decline this access. In addition, they
will be
are being
asked specifically and separately for permission about access to their Summary Care
[40 words unchanged]
Record will only ever be accessed on one occasion for each individual
participant/
participant.
Access is required for the period that the trial is recruiting
-
currently this is April
20
2020
until
Sept 21.
March 2023.
[2 paragraphs unchanged]
There will be no re-use of the data shared for direct care purposes for non-direct care
purposes.
purposes,
but the wider context for the use of the data is as part of a clinical trial.
Note that this is
This request for SCR access for PRINCIPLE, along with the similar request for the sister trial, PANORAMIC, together formed
a first of type access request and as an interim position it
is
was
included in the Data Sharing Agreement. This
is
continues to be
a holding position whilst considerations are undertaken to agree whether to offer
[42 words unchanged]
access process alongside the normal direct care process for access to SCR.
******************
FOLLOW UP DATA:
• Request to receive 28 day follow up data
(HES APC, HES Critical Care, GDPPR and Civil Registration of Deaths):
for:
The trial follows up all consented participants for 28 days. For the just under 4,500 participants currently recruited, data for 2,000 of the participants comes from the Royal College of General Practitioners (RCGP) Research and Surveillance Centre platform, but not all GPs are registered with this system. The trial team is currently contacting GPs to collect follow up data for the other 2,000 participants, which is a huge burden on team resource and a slow process.
> Hospital Episode Statistics (HES) Admitted Patient Care (APC)
> HES Critical Care (CC)
> Civil Registration (Deaths) data set
> GP Data for Pandemic Planning and Research (GDPPR)
***New request for version 5 of this agreement***
> Medicines dispensed in Primary Care (from the NHS Business Services Authority (NHSBSA) data)
The trial follows up all consented participants for 28 days. For the just over 9,700 participants currently recruited, data for 2,000 of the participants comes from the Royal College of General Practitioners (RCGP) Research and Surveillance Centre platform, but not all GPs are registered with this system. The trial team is currently contacting GPs to collect follow up data for the remaining participants, which is a huge burden on team resource and a slow process.
[5 paragraphs unchanged]
- If
it
the hospital attendance
was
not likely
unlikely
to be related to
COVID,
COVID-19,
what was the reason for the hospital visit?
- If it was COVID-19 related, did they receive oxygen while in hospital?
- Was the hospital attendance to visit A&E?
- Did they receive oxygen while in hospital?
[3 paragraphs unchanged]
- Is the participant still in hospital with this admission?
[2 paragraphs unchanged]
- Was the participant prescribed any antibiotics between the date of randomisation and day 28 of their follow-up (excluding any antibiotics that may have been given as part of the study intervention)?
- Was the participant taking antibiotics for an acute condition when they were randomised to PRINCIPLE?
- If
they were,
yes,
what was the name of the antibiotic?
- Wat was the reason for the antibiotic prescription?
- Was the participant prescribed any antibiotics between the date of randomisation and day 28 of their follow-up (exclude any antibiotics that may have been given as part of the study intervention)?
- If yes, what was the name of the antibiotic?
- What was the reason for the antibiotic prescription?
[1 paragraph unchanged]
(The above is to be sourced from the GDPPR data).
- Has the participant been prescribed inhaled medication containing corticosteroids in the past 6 months? (Exclude any inhaled corticosteroids that may have been given as part of the study intervention).
- What date was the participant last prescribed inhaled medication containing corticosteroids before they were randomised?
- Has the participant been in contact with their GP after randomisation and up to an including day 28 of their follow-up?
- If yes, how many times?
(The above is to be sourced from the GDPPR/***Medicines dispensed in Primary Care data (NHSBSA data) ***).
[7 paragraphs unchanged]
This consent will allow for the analysis of the longer term effects and symptoms on participants in the trial, by comparison of patients on usual care compared to those who received a PRINCIPLE trial treatment/intervention.
[1 paragraph unchanged]
**********
New Request for version 5 of this agreement:
***Request to add Medicines dispensed in Primary Care (NHSBSA data) dataset to the existing 28 day follow up data***:
This additional dataflow will support those already received to follow up consented patients for 28 days. Key secondary outcomes will be obtained from this data output i.e. consumption of antibiotics, which is required for the final analysis of each treatment arm used on the trial. Furthermore, resources such as staff and expense required for the manual process of collecting participant medical notes and reviews from GP practices is very costly, and having access to this data from NHS Digital would reduce the number of working hours previously needed to collect the data. The use of the Medicines dispensed in Primary Care (NHSBSA data) is in line with the direction which is to provide intelligence about the safety and effectiveness of medicines.
The NHSBSA data does encompass similarities to the GDPPR dataset already received as part of this agreement, however the NHSBSA provides extra information on the treatment prescribed beyond antibiotic, such as inhaled corticosteroid. Likewise, the medication data held within the GDPPR dataset provides information that can verify the data from medical notes review, therefore the study team have requested both the NHSBSA and GDPPR datasets for this agreement. The fields chosen within each dataset have been limited ensure that duplication of data is minimised.
As per the previous amendment for 28 follow up data, the existing consent covers the provision of this extra data and it will only be accessed by the team at University of Oxford, and no other organisations will process or store it.
LEGAL BASIS
The lawful basis for the release and use of the confidential data for Covid-19 UK Non-hospital Antigen Testing Results (pillar 2) being shared under this version of the agreement is Regulation 3(4) of the National Health Service (Control of Patient Information Regulations) 2002 (COPI) to require NHS Digital to share confidential patient information with organisations entitled to process this under COPI for COVID-19 purposes. The only permitted activities under this Data Sharing Agreement (DSA) are for COVID-19 purposes and within bounds of Reg 3(2) COPI. Reg 3 (2) COPI states that: "2) For the purposes of this regulation, “processing” includes any operations, or set of operations set out in regulation 2(2) which are undertaken for the purposes set out in paragraph (1)." The research relates to the monitoring and managing of COVID-19 and would therefore be covered by Reg 3(1)(d) of COPI.
NOTE: University of Oxford must rely on the COPI notice for the statutory sharing of information by NHS Digital for COVID-19 purposes. When the COPI notice expires, full support and approval for section 251 from the Confidentiality Advisory Group has been received and will supersede the COPI notice for the release and use of the confidential data (Covid-19 UK Non-hospital Antigen Testing Results (pillar 2) under this agreement.
Consent is in place to allow the access to Summary Care Record (SCR) data and dissemination of pseudonymised follow-up data to be provided to the study team from NHS Digital. Details of the trial and expected data flows are explained on the latest version of Patient Information Sheet which will be hosted on the trial website: https://www.principletrial.org/
Only the study team at the University of Oxford will access the requested NHS Digital record-level data. No other organisations are involved in the processing or storage of NHS Digital record level data. NHS Digital record level data will not leave the UK.
LEGAL BASIS FOR PROCESSING DATA
The University of Oxford, as the Data Controller who is also processing the data will process Personal data under GDPR Article 6 (1) (e) - Processing is necessary for the performance of a task carried out in the public interest or in the exercise of official authority vested in the controller. As a higher education establishment, the University conduct research to improve health care and service and the data requested is necessary for the performance of a task carried out in the public interest.
The trial is of national and international relevance during this pandemic. The primary focus of the trial is treatment of confirmed (PCR positive) SARS-CoV2 infections to speed up recovery, prevent hospitalisation and/or death and reduce symptoms, thus reducing clinical impact of the virus on individuals and the strain on NHS hospitals, thus research very much in the public interest.
Additionally, under GDPR Article 9(2)(j) processing of Special Category Personal Data (of which Health data is one) is necessary for archiving for research purposes. Data minimisation process is being followed and only data that is required specifically for the purposes of this study has been requested, to protect the rights of the data subjects. The data are required for research purposes in the public interest – meeting the conditions in the DPA 2018 Schedule 1 Part 1 (4) – which GDPR Recital 52(2) determines is an appropriate derogation from the prohibition on processing special categories of personal data.
Article 9(2)(h) is additionally being used to cover the processing of SCR specifically: ‘processing is necessary for the purposes of preventive or occupational medicine, for the assessment of the working capacity of the employee, medical diagnosis, the provision of health or social care or treatment or the management of health or social care systems and services’ as it is being used as a timely, second check regarding medication, allergy, and co-morbidities information to support reconciliation, to ensure safe prescribing.
In accordance with GDPR Article 89(1) processing is subject to appropriate safeguards. These include:
- The data recipient’s technical and organisational measures to safeguard the data have been assessed and meet NHS Digital’s acceptance criteria (see sections 2 and 5b of this application for further details;
- The requested data has been assessed as proportionate to the aim pursued (see section 5a of this application for further details);
Controls, data retention and processing activities have been assessed to ensure respect to the essence of the right to data protection (see sections 5a, 5b and 8a of this application for further details);
- Measures to protect the rights and freedoms of data subjects have been assessed including transparency (fair processing) publishing subject’s rights to withdraw consent and /or have their data erased or rectified, etc.
The PRINCIPLE trial is funded by the National Institute of Health Research (NIHR) and UK Research and Innovation (UKRI) Medical Research Group (MRC). NIHR and UKRI MRC do not make any decisions determining the purposes and means of the processing of data or the study purpose and methodology, and are therefore not considered as Data Controllers. Additionally, the NIHR and UKRI MRC will not have access to any NHS Digital record level data and are therefore not considered as Data Processors.
A collaborator agreement is in place between University of Oxford and the institutions listed on the protocol for this clinical trial. The study team have confirmed that the institutions listed within the protocol will not have access to NHS Digital record level data and therefore, in line with NHS Digital’s DARS standards, does not consider these other institutions as joint Data Controllers or Data Processors for this agreement.
Processing activities
The trial is run remotely, therefore removing the need for participants to
[6 words unchanged]
Screening and contact with the trial team is all done online. The
trial
study
team
will, however, contact
have requested access to
the
participant’s GP for information from their
participants
summary care record, to ensure safe prescribing – for example, that they will not be allergic to the proposed treatments.
The trial team may however contact the participant’s GP should any concerns arise regarding uncertainties with the information provided within the participants Summary Care Record, or should the participant not consent for access to the SCR. The Patient Information Sheet states:
The processing of the data will be as follows:
“We will ask for your consent to view your SCR. The SCR will not be retained by the trial team. If your SCR is unavailable or you do not consent for us to access it, you can still take part in the trial as we will obtain this information from your GP.”
• On a daily basis (seven days a week) NHS Digital will interrogate the Pillar 2 dataset and extract up to 500 individuals at random who are 50 or over who have received a positive COVID 19 test result in the previous 24 hours.
Covid-19 UK Non-hospital Antigen Testing Results (pillar 2) - The processing of the data will be as follows:
• The individuals will be England-only.
• On a daily basis (seven days a week) NHS Digital will interrogate the Pillar 2 dataset and extract up to 500 individuals at random who are aged 18 or over who have received a positive COVID-19 test result in the previous 24 hours.
• Filters will be applied to remove patients who have registered a national opt-out, as well as special categories of people for whom the data should not be disseminated, such as prisoners.
• The individuals will be residents of England-only.
• Individuals who have signed up for the Telephone Preference Service will need to be taken into account.
• Filters will be applied to remove patients who have registered a National Data Opt-Out, as well as special categories of people for whom the data should not be disseminated. The purpose of the restriction is to ensure that patient information that might imply a location is protected.
• The flow from NHS Digital to University of Oxford will be automated via a SEFT account.
• Individuals who have signed up for the Telephone Preference Service will not be contacted via telephone.
• University of Oxford will use the data provided to make outbound to ask if the individuals would be interested in being recruited into the trial.
• The flow from NHS Digital to University of Oxford will be automated via a Secure Electronic File Transfer service (SEFT.)
• University of Oxford will use the data provided to make outbound communications to ask if eligible individuals would be interested in being recruited into the trial.
[2 paragraphs unchanged]
The trial team in Oxford will hold the data securely adhering to all
IG
Information Governance (IG)
Policies in the
Dept., the
department. The trial
team will call these contacts to inform them of the trial, screen, consent and randomise them.
[1 paragraph unchanged]
********************
Statistical data analysis will be carried out via University of Oxford owned devices connected to the University of Oxford network either directly in person or remotely, using an appropriate statistical package. To remotely access the devices requires a secure 2-factor authenticator (VPN) and users are then able to securely access the secure server on the University’s IT framework. All data analysis will be conducted within the confines of the University’s secure server, and will not be downloaded to remote devices for storage or processing.
• Request to use SCR for consented participants:
Berry Consultancy in the USA will also be undertaking data analysis, however this will be performed using non-NHS Digital data. No NHS Digital record-level data will be processed by any organisation not already stated in this agreement, nor will any NHS Digital record-level data be sent, stored or processed outside of the UK.
As per section 5A, once participants are recruited into PRINCIPLE, the trial team will access their Summary Care Record. This will be through ‘SCR Core’ or ‘SCR Additional Information’, depending on what is available for each participant.
• Request to use Summary Care Record (SCR) for consented participants:
Once participants are recruited into PRINCIPLE, the trial team will access their Summary Care Record. This will be through ‘SCR Core’ or ‘SCR Additional Information’, depending on what is available for each participant.
[11 paragraphs unchanged]
The Clinical trial team will use
SCRa
SCR
and build on best practice by identifying the patient’s NHS number after
[23 words unchanged]
being returned to the patient’s practice regarding their participation in the trial.
[2 paragraphs unchanged]
• Request to receive 28 day follow up data (HES APC, HES Critical Care, GDPPR, ***Medicines dispensed in Primary Care data*** and Civil Registration of Deaths):
On a monthly basis the trial team will send to NHS Digital the relevant data items for those cohort members who have hit the 28 day follow up window.
The University of Oxford will provide NHS Digital with the following information via Secure Electronic File Transfer (SEFT) for consented participants:
• Study ID
• NHS Number
• Date of Birth
• Trial recruitment date
• withdrawal date (if applicable)
NHS Digital will link the cohort members to the aforementioned datasets and return the record-level pseudonymised outputs to the Study team at the University of Oxford via SEFT.
NHS Digital Record Level Data will not be linked to any other datasets.
One of the data sets requested in this agreement (GPES Data for Pandemic Planning and Research - GDPPR) has been collected under a specific COVID-19 related direction, and as such can only be used for COVID-19 research related purposes. The COPI notice that will cover this flow of data is currently set to expire on 30 June 2022.
[1 paragraph unchanged]
• Request to receive 28 day follow up data (HES APC, HES Critical Care, GDPPR and Civil Registration of Deaths):
New Request for version 5 of this agreement:
On a monthly basis the trial team will send to NHs Digital the relevant data items for those cohort members who have hit the 28 day follow up window.
*** Request to add Medicines dispensed in Primary Care (NHSBSA data) dataset to the existing 28 day follow up data***
The following data items will be provided for linkage: Study ID, NHS Number, Date of Birth.
• In addition to the previous request for 28 day follow up data, data from the Medicines dispensed in Primary Care (NHSBSA data) dataset will be linked to the cohort and provided to University of Oxford on a monthly basis and in line with the existing transfer and security arrangements.
NHS Digital will link the cohort members to the aforementioned datasets and return the outputs to the team via Secure Electronic File Transfer [SEFT].
HES and ECDS DISCLOSURE CONTROL / SMALL NUMBER SUPPRESSION
One of the data sets requested in this application (GPES Data for Pandemic Planning and Research - GDPPR) has been collected under a specific COVID-19 related direction, and as such can only be used for COVID-19 research related purposes. The COPI notice that will cover this flow of data is currently set to expire at the same time as this agreement.
In order to protect patient confidentiality, when presenting results calculated from HES record level data, outputs will contain only aggregate level data with small numbers suppressed in line with HES Analysis Guide. When publishing HES data, data processors must make sure that:
• National-level figures only may be presented unrounded, without small number suppression
• cell values from 1 to 7 (inclusive) are suppressed at a sub-national level to prevent possible identification of individuals from small counts within the table.
• Zeros (0) do not need to be suppressed.
• All other counts will be rounded to the nearest 5.
Data will not be made available to any third parties other than those specified except in the form of aggregated outputs with small numbers suppressed in line with the HES Analysis Guide.
Expected output
The Principle/PANORAMIC trial will recruit to target much quicker than using current methods if the team can receive this data; the statistical team will receive follow up data in a more timely manner, therefore answering the covid-19 treatment in the community question more quickly with the aim of preventing covid-19 patients being hospitalised so reducing NHS burden.
All outputs will be aggregated with small number suppression applied as per the HES analysis guide.
It appears to take between 800-1200 patients per arm to answer the question for the drug of that arm. 1500 per arm is the target recruitment number, and just over 6000 patients have been recruited at the time of the third amendment to this agreement. Five arms have been closed so far, leaving two arms open, with more arms to follow thereafter.
The PRINCIPLE trial should be able to recruit to target much quicker than using current methods if the team can receive the requested NHS Digital identifiable data. The statistical team will aim to receive follow up data in a more timely manner, therefore answering the COVID-19 treatment in the community question more quickly with the aim of preventing covid-19 patients being hospitalised so in turn reducing NHS burden.
The trial team will ensure that trial results are disseminated to all relevant parties (regular updates to the Therapeutic Taskforce, UPH committee, NIHR, DHSC) and dissemination via media channels and to trial participants, supported by the University of Oxford. Publications will be produced as quickly as possible.
It appears to take between 800-1200 patients per arm to answer the question for the drug of that arm. 1500 per arm is the target recruitment number, and just over 9,700 patients have been recruited at the time of the fifth amendment to this agreement. Five arms have been closed so far, leaving two arms open, with potential for more arms to follow thereafter.
The trial team intends to disseminate results via media channels: pre-prints/publications in peer-reviewed journals such as The Lancet, press releases in local and national newspapers; BBC news coverage; Department of Health and Social Care (DHSC) press briefings; DHSC Social media updates; Twitter and Facebook University of Oxford accounts. The study team intend to disseminate results to trial participants via the trial website, supported by the University of Oxford. The study team plan to provide regular updates to the NIHR Evaluation, Trials and Studies Coordinating Centre.
The study team intend to update participants by signposting them from their ‘end of trial letter’ to the trial website for the latest results and information. Due to the limited resources of the study trial team and the potential number of study participants involved, the study trial team have made the decision that distributing newsletters or email updates would be difficult to manage at such a scale. The study trial team believe that signposting to the website also ensures that the most up to date information is always available to participants, as newsletters can soon become outdated due to the fast-paced and evolving nature of this platform trial. The study team are also considering the use of video/audio updates and other formats to the website depending on capacity.
[1 paragraph unchanged]
Expected measurable benefits
The trial has co-primary endpoints: 1) Time taken to self-reported recovery; and 2) hospitalisation and/or death due to confirmed SARS-CoV-2 infection.. The main objective of the trial is to assess the effectiveness of the interventions in reducing time to recovery and in reducing the incidence of hospitalisation and/or death for COVID-19 patients.
COVID-19 treatments in the community, if deployed rapidly, have the potential to prevent transmission, reduce symptoms and hospitalisations, all of which hope to protect the vital gains of the vaccination programme, particularly if new variants of concern emerge which reduce vaccine efficacy. The emergence of the SARS-CoV2 virus has had a profound impact on the UK population. It is vital to ensure that a significant rise in infections and spread of the virus in the population is controlled as far as possible. The identification of treatments is integral to a longer-term response to COVID-19 and should enhance pandemic preparedness in the years ahead.
Key secondary outcomes include: Hospital assessment without admission; Oxygen administration; Intensive Care Unit admission; Mechanical ventilation (components of the WHO Ordinal Scale); Duration of hospital admission; Duration of severe symptoms; Sustained recovery; Contacts with the health services; Consumption of antibiotics; Effects in those with a positive test for COVID-19 infection; WHO Well-being Index.
The primary focus of the trial is treatment of confirmed (PCR positive) SARS-CoV2 infections to speed up recovery, prevent hospitalisation and/or death and reduce symptoms, thus reducing clinical impact of the virus on individuals and the strain on NHS hospitals.
Original target date
-
was to
recruit 3,000
participants
by
Dec
December
2020.
New
The study team now have a new
target to continue recruiting beyond the
6,500
9,700
patients already
recruited at time of the third amendment to this agreement in September 2021.
recruited.
Benefits reported
PRINCIPLE is the world’s largest Phase 3 platform randomised controlled trial of
[64 words unchanged]
progress, investigating seven potential COVID-19 treatments in 18 months, recruiting more than
6500 participants.
9,700 participants .
PRINCIPLE has successfully identified budesonide as the first
widely available,
previously licensed,
inexpensive COVID-19 treatment, which the Chief Medical Officer has recommended on a
[63 words unchanged]
minority and socioeconomically deprived participants to national figures for its target population.
[1 paragraph unchanged]
DARS-NIC-411161-G4K7X-v4.4 2 October 2021 to 31 March 2022
- Title
- PRINCIPLE: Platform Randomised Trial of Treatments in the Community for Epidemic and Pandemic Illnesses/ PANORAMIC: Platform Adaptive trial of NOvel antiviRals for eArly treatMent of covid-19 In the Community
- Commercial
- No
- Sublicensing
- No
- Datasets
- 6
- Files released
- 20
Datasets: Civil Registrations of Death; COVID-19 Access to Summary Care Records; COVID-19 General Practice Extraction Service (GPES) Data for Pandemic Planning and Research (GDPPR); COVID-19 UK Non-hospital Antigen Testing Results (Pillar 2); Hospital Episode Statistics Admitted Patient Care (HES APC); Hospital Episode Statistics Critical Care (HES Critical Care)
What changed from DARS-NIC-411161-G4K7X-v3.2
Text removed is struck through; text added is underlined. Unchanged paragraphs are summarised rather than repeated.
| Field | Was | Became |
|---|---|---|
| Title | PRINCIPLE: Platform Randomised Trial of Treatments in the Community for Epidemic and Pandemic Illnesses/ PANORAMIC: Platform Adaptive trial of NOvel antiviRals for eArly treatMent of covid-19 In the Community | |
| Start date | 2021-10-02 | |
| End date | 2022-03-31 | |
| Civil Registrations of Death: type of data | Anonymised - ICO Code Compliant | |
| Hospital Episode Statistics Admitted Patient Care (HES APC): type of data | Anonymised - ICO Code Compliant | |
| Hospital Episode Statistics Critical Care (HES Critical Care): type of data | Anonymised - ICO Code Compliant |
Expected output
The
Principle
Principle/PANORAMIC
trial will recruit to target much quicker than using current methods if
[31 words unchanged]
the aim of preventing covid-19 patients being hospitalised so reducing NHS burden.
It appears to take between 800-1200 patients per arm to answer the
[5 words unchanged]
that arm. 1500 per arm is the target recruitment number, and just
under 4500
over 6000
patients have been recruited at the time of the
second
third
amendment to this agreement.
Three
Five
arms have been closed so far, leaving two arms
open. Another arm will open late February and another arm in early March,
open,
with more arms to follow thereafter.
The trial team will ensure that trial results are disseminated to all relevant parties (regular updates to the Therapeutic Taskforce, UPH committee, NIHR,
DoHSC)
DHSC)
and dissemination via media channels and to trial participants, supported by the University of Oxford. Publications will be produced as quickly as possible.
[1 paragraph unchanged]
Expected measurable benefits
The trial has co-primary endpoints: 1) Time taken to self-reported recovery; and 2) hospitalisation and/or
death.
death due to confirmed SARS-CoV-2 infection..
The main objective of the trial is to assess the effectiveness of
[5 words unchanged]
to recovery and in reducing the incidence of hospitalisation and/or death for
covid-19
COVID-19
patients.
[1 paragraph unchanged]
Original target date - recruit 3,000 by Dec 2020. New target to continue recruiting beyond the
4,500
6,500
patients already recruited at time of
second
the third
amendment to this agreement in
March
September
2021.
Benefits reported
Not stated in the previous version; added here.
PRINCIPLE is the world’s largest Phase 3 platform randomised controlled trial of possible COVID-19 treatments for recovery at home. The trial has evolved to represent the first ‘democratic', nationally inclusive trial of an acute condition in the UK, through the use of online consent, remote eligibility checking, remote randomisation, online/telephone follow-up and central distribution of study materials direct to the participant. PRINCIPLE has proven ability to suspend and add treatment arms while the study is in progress, investigating seven potential COVID-19 treatments in 18 months, recruiting more than 6500 participants. PRINCIPLE has successfully identified budesonide as the first widely available, inexpensive COVID-19 treatment, which the Chief Medical Officer has recommended on a case-by-case basis. The results have also shown that azithromycin and doxycycline are not generally effective treatments for COVID-19. The UK-wide opportunity to contribute to this research has been a major transformative achievement for the trial. PRINCIPLE is especially committed to reaching disadvantaged populations, typically under-researched, with a trial National Pharmacy and Ethnic Minority Communities Research Lead. It has achieved comparable representations for ethnic minority and socioeconomically deprived participants to national figures for its target population.
PRINCIPLE was recognised by the ‘Health Data Research UK (HDR UK) Impact of the Year Award 2021’ as a leading example of the innovative use of primary care data whilst working at pace and scale. The trial has successfully co-ordinated data flows from over 3100 GP sites (including Notes Review Case Report Forms (CRF) completed by GPs at trial sites), combined with routinely collected electronic NHS data through partnership with the NHS Digital Information Governance Team, the Information Commissioner’s Office, NHS Test & Trace, NHS DigiTrials Health Data Research (HDR) Hub, the Department of Health and Social Care (DHSC), and the HDR UK Public & Patient Involvement and Engagement Team, to obtain data as close to real-time as possible, with primary outcome data available for 95% of participants.
Unchanged: Objective for processing, Processing activities.
Objective for processing
Over recent weeks, there has been an increase in the number of COVID-19 cases in the community and in hospitalisation. Currently, there are no treatments that have been proven in rigorous trials to help people with COVID-19 symptoms in the community recover quicker and reduce the need for hospital admission. It is therefore vital that the University of Oxford use this opportunity to accelerate enrolment into COVID-19 therapeutics trials.
The PRINCIPLE (Platform Randomised trial of Interventions against COVID-19 In older peoPLE) trial is the only national Urgent Public Health priority clinical trial evaluating potential therapeutics for COVID-19 in the primary care setting, endorsed by the CMOs of all four devolved nations . The trial aims to find out whether early treatment in the community speeds recovery and reduces the need for hospital admission for those with COVID-like-Illness.
PRINICIPLE is:
• Recruiting across the whole UK: anyone can participate, regardless of location.
• Light burden for both recruiters and patients; it only takes couple of minutes to complete enrolment on to the trial.
• Obtaining consent, checking eligibility, issuing study medication and materials, and follow-up is manged remotely through a central facility.
Primary objective - To assess effectiveness of trial treatments in reducing the need for hospital admission or death, for patients aged ≥50 years with comorbidity, and aged ≥65 with or without comorbidity and suspected COVID-19 infection during time of prevalent COVID-19 infections.
Secondary objectives - To explore whether trial treatment reduces
1) Duration of severe symptoms
2) Time taken to self-report recovery
3) Contacts with the health services
4) Consumption of antibiotics
5) Hospital assessment without admission
6) Oxygen administration
7) Intensive Care Unit admission
8) Mechanical ventilation
9) To determine if effects are specific to those with the infections syndrome but who test positive for COVID-19
10) Duration of hospital admission
The trial was initially only recruiting via GP practices and the website and had c. 1000 participants when use of the Pillar 2 data was first proposed in in order to rapidly increase this to 3,000 (and beyond to support further trial arms). At the time of the second amendment for 28 day follow up data (while also continuing receiving Pillar 2 data) just under 4,5000 patients had been recruited.
The University of Oxford would like to receive names and contact details (preferably a telephone number) of people who have received a positive covid-19 swab result from the Pillar 2 testing system. The trial team based in Oxford will then contact these potential participants, inform them about the trial and if they are happy, go on to screen and consent them into Principle. Daily, the trial team would like to receive data on a random cohort (initially 200, now up to 500) of people aged 50+. They may need to increase this age to 65+ if those they contact screen as ineligible for the trial as they lack the required comorbidities.
Consideration has been given to whether the trial should be contacting individuals directly, and whether the recruitment could be managed through the Test and Trace service, i.e. the service are already set up to contact individuals and could inform them of the trial when they get in touch. However, given the use of contractors to operate this service, and thereby creating an extra layer to the process, this is unlikely to fit with the timescales the trial are working to (which ties in with why they have decided to switch from GPs as the primary source of recruitment). Additionally, the trial already has a centre set up and operating remotely to manage this recruitment in a timely manner.
The question of whether ‘cold calling’ is appropriate has been considered for this application, especially against alternatives such as SMS and emailing. As time is of the essence for recruitment into PRINCIPLE, telephone is the most efficient and quickest means to ensure direct contact with the individual, who can answer questions instantly over a call. This also ensures ‘human contact’, as opposed to SMS / emails, with trained and experienced CTU research nurses working directly to the trial team providing that contact. During the calls, clear explanation will be given to individual about how the trial has been able to contact them and what to do if they do not wish to be contacted again (i.e. registering a national opt-out). The trial team will decide whether to apply the Telephone Preference Service under their own discretion. The trial team will also ensure the required comorbidities are discussed early on in the calls so as to not to get the individual’s hopes up if they are not in fact eligible for the trial. Lessons have been learned from a recent NHS Digital request for contact details provided to researchers contact people to donate blood and plasma, with careful attention paid to the various take up rates and any changes rates in these between the first and second waves of the pandemic. However, unlike that trial, PRINCIPLE could potentially be of direct benefit to the individual.
Other considerations that have been taken into account in relation to contacting individuals:
• The data relating to positive COVID19 tests is sent to NHS Digital at the same time that it is sent to the Business Services Authority, the latter process triggering the SMS to the individual informing them of their result. It then takes around four hours for the Pillar 2 dataset within NHS Digital to be updated with this information. Given that this information then needs to be extracted from the dataset at some point in the next 24 hours, then used by the trial team to make contact with the individual, the risk of the individual being informed of their test result by the trial team before they have read their SMS is small. However, the trial team should have a suitable script prepared to deal with this slim possibility.
• The chances of people having multiple positive COVID19 test results are rare, and rarer still is the likelihood that they will be one of the 500 people extracted from the thousands of daily test results to be sent to the trial team on more than one occasion. Therefore the risk of an individual being contacted twice for recruitment into PRINCIPLE is extremely low.
• NHS Digital recognises that there are likely to be more requests of this nature in future and therefore, if multiple trial require extracts of people to contact, suitable controls need to be in place within the extract process to ensure that individuals are not getting contacted for recruitment into trials more than is reasonably expected.
********************
• Request to use SCR for consented participants:
Supplementary to the requirement to receive Pillar 2 data for recruitment into PRINCIPLE, the trial team will access the Summary Care Record (SCR) of all patients recruited into the trial for the purposes of ensuring timely prescribing and safe patient care.
Currently, up to 40% of people who provide consent to participate in the PRINCIPLE Trial are delayed in starting their trial medication, or are effectively denied the opportunity to participate because of delays in checking information concerning their eligibility to safely be given the study treatments. Because so many people who are keen to contribute are being lost to the PRINCIPLE Trial, crucial study results are not yet forthcoming. If processes around ensuring timely, safe prescribing and patient care could be enhanced, then time to potentially life-saving trial results will be reduced.
The purpose of this request is therefore to seek permission for the clinical trial team, a group of dedicated doctors and nurses who are fully qualified, study-trained, accredited and registered, to review consenting patients’ Summary Care Records, in order to be able to confirm key information obtained from the patient relevant to safe patient care in the trial. Only nurses and doctors who are qualified, trained and fully registered and accredited with the General Medical Council of the UK or the Nursing and Midwifery Council of the UK who are clinical members of the PRINCIPLE Study team would review the Summary Care Record for information relevant to safe prescribing and participant care.
The Summary Care Record will be used as a timely, second check regarding medication, allergy, and co-morbidities information to support reconciliation, to ensure safe prescribing. These are all elements of a patient’s SCR with additional information which is a subset of their wider GP record. This access provides an immediate available information source to meet the need to support safe prescribing in a proportionate and timely way. In addition, the Summary Care Record will provide a further safety check, in that access to it will facilitate the opportunity for double-checking participants’ NHS Number and GP practice.
Current PRINCIPLE Trial procedures involve the clinical trial team endeavouring to identify a consenting patient’s GP, emailing or posting the participant’s consent form to the GP to obtain relevant clinical information for the study clinical team to confirm eligibility, then waiting for the GP to send selected summary clinical information from the patient’s record back to the trial clinical team, before it is then checked against patient-reported information. This proportionate access also minimises the burden on frontline general practice at a time of considerable pressures.
Access is sought only for those people who have screened eligible to be part of the Trial, and who have already signed informed consent for participation in the study and for the Trial to access their clinical records. All potential participants are asked specifically for permission for the trial team to access their medical records and have the opportunity to decline this access. In addition, they will be asked specifically and separately for permission about access to their Summary Care Record. For a patient who has provided consent to join the trial and for their SCR to be accessed, the data will be accessed by a clinician to support safe prescribing decisions immediately prior to prescribing medications. A Summary Care Record will only ever be accessed on one occasion for each individual participant/
Access is required for the period that the trial is recruiting currently this is April 20 until Sept 21.
• Access in relation the purposes of direct care:
The purpose of SCR is to allow healthcare professionals to check relevant facts prior to carrying out direct care of an individual. The clinical trial will support direct care in this use case as healthcare professionals are carrying out direct care (avoiding dangerous prescribing) for individuals, with the patient’s consent.
There will be no re-use of the data shared for direct care purposes for non-direct care purposes. but the wider context for the use of the data is as part of a clinical trial.
Note that this is a first of type access request and as an interim position it is included in the Data Sharing Agreement. This is a holding position whilst considerations are undertaken to agree whether to offer this as a service more widely to clinical trials for patient safety purposes. This allows time for an appropriate access and approval process to be developed in future, but in the meantime ensures that SCR access is recognised within the research data access process alongside the normal direct care process for access to SCR.
******************
• Request to receive 28 day follow up data (HES APC, HES Critical Care, GDPPR and Civil Registration of Deaths):
The trial follows up all consented participants for 28 days. For the just under 4,500 participants currently recruited, data for 2,000 of the participants comes from the Royal College of General Practitioners (RCGP) Research and Surveillance Centre platform, but not all GPs are registered with this system. The trial team is currently contacting GPs to collect follow up data for the other 2,000 participants, which is a huge burden on team resource and a slow process.
Due to the high rate of recruitment, the Data Safety Committee review the trial data weekly and can ask for recruitment into a trial arm to be stopped immediately. Therefore trial data needs to be made available as soon as possible so that the team can quickly issue a press statement and publication of results if required to do so. To date, there have been three trial arms stopped, essentially because all required data has not been available immediately and it has taken the team too long to collect that data and issue the information publicly. There is therefore a need to capture the required data in a more timely and efficient manner via monthly extracts from NHS Digital.
Data required is as follows:
- Did the participant attend a hospital for medical reasons between the date of randomisation and day 28 of their follow-up?
- What date did they go to hospital?
- Was this attendance likely related to COVID-19?
- If it was not likely to be related to COVID, what was the reason for the hospital visit?
- If it was COVID-19 related, did they receive oxygen while in hospital?
- Did they receive mechanical ventilation while in hospital?
- Were they admitted overnight?
- If yes, how many nights did they stay in hospital?
- Did they stay in an Intensive Care Unit during their stay in hospital?
(The above is to be sourced from the HES APC and Critical Care data).
- Was the participant prescribed any antibiotics between the date of randomisation and day 28 of their follow-up (excluding any antibiotics that may have been given as part of the study intervention)?
- If they were, what was the name of the antibiotic?
- Wat was the reason for the antibiotic prescription?
- What was the start date of antibiotic course?
(The above is to be sourced from the GDPPR data).
- Has the participant died?
- If yes, what was the date of death?
- What was the cause of death?
- Did COVID-19 contribute to death?
(The above is to be sourced from the Civil Registration of Deaths data).
Consent is in place to allow this data to be provided to the team from NHS Digital and is contained on the latest version of Patient Information Sheet on the trial website (https://www.principletrial.org/participants/participant-information-sheets):
“In addition, we will collect information from your GP records and data held by central NHS bodies (such as NHS Digital) for long-term follow-up for up to 10 years, to help us better understand the long-term effects of COVID-19 and the trial treatments.”
Only the team at the University of Oxford will access this data. No other organisations are involved in the processing or storage.
Expected output
The Principle/PANORAMIC trial will recruit to target much quicker than using current methods if the team can receive this data; the statistical team will receive follow up data in a more timely manner, therefore answering the covid-19 treatment in the community question more quickly with the aim of preventing covid-19 patients being hospitalised so reducing NHS burden.
It appears to take between 800-1200 patients per arm to answer the question for the drug of that arm. 1500 per arm is the target recruitment number, and just over 6000 patients have been recruited at the time of the third amendment to this agreement. Five arms have been closed so far, leaving two arms open, with more arms to follow thereafter.
The trial team will ensure that trial results are disseminated to all relevant parties (regular updates to the Therapeutic Taskforce, UPH committee, NIHR, DHSC) and dissemination via media channels and to trial participants, supported by the University of Oxford. Publications will be produced as quickly as possible.
The trial is of national and international relevance during this pandemic.
Benefits reported
PRINCIPLE is the world’s largest Phase 3 platform randomised controlled trial of possible COVID-19 treatments for recovery at home. The trial has evolved to represent the first ‘democratic', nationally inclusive trial of an acute condition in the UK, through the use of online consent, remote eligibility checking, remote randomisation, online/telephone follow-up and central distribution of study materials direct to the participant. PRINCIPLE has proven ability to suspend and add treatment arms while the study is in progress, investigating seven potential COVID-19 treatments in 18 months, recruiting more than 6500 participants. PRINCIPLE has successfully identified budesonide as the first widely available, inexpensive COVID-19 treatment, which the Chief Medical Officer has recommended on a case-by-case basis. The results have also shown that azithromycin and doxycycline are not generally effective treatments for COVID-19. The UK-wide opportunity to contribute to this research has been a major transformative achievement for the trial. PRINCIPLE is especially committed to reaching disadvantaged populations, typically under-researched, with a trial National Pharmacy and Ethnic Minority Communities Research Lead. It has achieved comparable representations for ethnic minority and socioeconomically deprived participants to national figures for its target population.
PRINCIPLE was recognised by the ‘Health Data Research UK (HDR UK) Impact of the Year Award 2021’ as a leading example of the innovative use of primary care data whilst working at pace and scale. The trial has successfully co-ordinated data flows from over 3100 GP sites (including Notes Review Case Report Forms (CRF) completed by GPs at trial sites), combined with routinely collected electronic NHS data through partnership with the NHS Digital Information Governance Team, the Information Commissioner’s Office, NHS Test & Trace, NHS DigiTrials Health Data Research (HDR) Hub, the Department of Health and Social Care (DHSC), and the HDR UK Public & Patient Involvement and Engagement Team, to obtain data as close to real-time as possible, with primary outcome data available for 95% of participants.
DARS-NIC-411161-G4K7X-v3.2 4 May 2021 to 1 October 2021
- Title
- PRINCIPLE: Platform Randomised trial of INterventions against COVID-19 In older peoPLE
- Commercial
- No
- Sublicensing
- No
- Datasets
- 6
- Files released
- 18
Datasets: Civil Registrations of Death; COVID-19 Access to Summary Care Records; COVID-19 General Practice Extraction Service (GPES) Data for Pandemic Planning and Research (GDPPR); COVID-19 UK Non-hospital Antigen Testing Results (Pillar 2); Hospital Episode Statistics Admitted Patient Care (HES APC); Hospital Episode Statistics Critical Care (HES Critical Care)
What changed from DARS-NIC-411161-G4K7X-v2.5
Text removed is struck through; text added is underlined. Unchanged paragraphs are summarised rather than repeated.
| Field | Was | Became |
|---|---|---|
| Start date | 2021-05-04 |
Unchanged: Objective for processing, Processing activities, Expected output, Expected measurable benefits.
Objective for processing
Over recent weeks, there has been an increase in the number of COVID-19 cases in the community and in hospitalisation. Currently, there are no treatments that have been proven in rigorous trials to help people with COVID-19 symptoms in the community recover quicker and reduce the need for hospital admission. It is therefore vital that the University of Oxford use this opportunity to accelerate enrolment into COVID-19 therapeutics trials.
The PRINCIPLE (Platform Randomised trial of Interventions against COVID-19 In older peoPLE) trial is the only national Urgent Public Health priority clinical trial evaluating potential therapeutics for COVID-19 in the primary care setting, endorsed by the CMOs of all four devolved nations . The trial aims to find out whether early treatment in the community speeds recovery and reduces the need for hospital admission for those with COVID-like-Illness.
PRINICIPLE is:
• Recruiting across the whole UK: anyone can participate, regardless of location.
• Light burden for both recruiters and patients; it only takes couple of minutes to complete enrolment on to the trial.
• Obtaining consent, checking eligibility, issuing study medication and materials, and follow-up is manged remotely through a central facility.
Primary objective - To assess effectiveness of trial treatments in reducing the need for hospital admission or death, for patients aged ≥50 years with comorbidity, and aged ≥65 with or without comorbidity and suspected COVID-19 infection during time of prevalent COVID-19 infections.
Secondary objectives - To explore whether trial treatment reduces
1) Duration of severe symptoms
2) Time taken to self-report recovery
3) Contacts with the health services
4) Consumption of antibiotics
5) Hospital assessment without admission
6) Oxygen administration
7) Intensive Care Unit admission
8) Mechanical ventilation
9) To determine if effects are specific to those with the infections syndrome but who test positive for COVID-19
10) Duration of hospital admission
The trial was initially only recruiting via GP practices and the website and had c. 1000 participants when use of the Pillar 2 data was first proposed in in order to rapidly increase this to 3,000 (and beyond to support further trial arms). At the time of the second amendment for 28 day follow up data (while also continuing receiving Pillar 2 data) just under 4,5000 patients had been recruited.
The University of Oxford would like to receive names and contact details (preferably a telephone number) of people who have received a positive covid-19 swab result from the Pillar 2 testing system. The trial team based in Oxford will then contact these potential participants, inform them about the trial and if they are happy, go on to screen and consent them into Principle. Daily, the trial team would like to receive data on a random cohort (initially 200, now up to 500) of people aged 50+. They may need to increase this age to 65+ if those they contact screen as ineligible for the trial as they lack the required comorbidities.
Consideration has been given to whether the trial should be contacting individuals directly, and whether the recruitment could be managed through the Test and Trace service, i.e. the service are already set up to contact individuals and could inform them of the trial when they get in touch. However, given the use of contractors to operate this service, and thereby creating an extra layer to the process, this is unlikely to fit with the timescales the trial are working to (which ties in with why they have decided to switch from GPs as the primary source of recruitment). Additionally, the trial already has a centre set up and operating remotely to manage this recruitment in a timely manner.
The question of whether ‘cold calling’ is appropriate has been considered for this application, especially against alternatives such as SMS and emailing. As time is of the essence for recruitment into PRINCIPLE, telephone is the most efficient and quickest means to ensure direct contact with the individual, who can answer questions instantly over a call. This also ensures ‘human contact’, as opposed to SMS / emails, with trained and experienced CTU research nurses working directly to the trial team providing that contact. During the calls, clear explanation will be given to individual about how the trial has been able to contact them and what to do if they do not wish to be contacted again (i.e. registering a national opt-out). The trial team will decide whether to apply the Telephone Preference Service under their own discretion. The trial team will also ensure the required comorbidities are discussed early on in the calls so as to not to get the individual’s hopes up if they are not in fact eligible for the trial. Lessons have been learned from a recent NHS Digital request for contact details provided to researchers contact people to donate blood and plasma, with careful attention paid to the various take up rates and any changes rates in these between the first and second waves of the pandemic. However, unlike that trial, PRINCIPLE could potentially be of direct benefit to the individual.
Other considerations that have been taken into account in relation to contacting individuals:
• The data relating to positive COVID19 tests is sent to NHS Digital at the same time that it is sent to the Business Services Authority, the latter process triggering the SMS to the individual informing them of their result. It then takes around four hours for the Pillar 2 dataset within NHS Digital to be updated with this information. Given that this information then needs to be extracted from the dataset at some point in the next 24 hours, then used by the trial team to make contact with the individual, the risk of the individual being informed of their test result by the trial team before they have read their SMS is small. However, the trial team should have a suitable script prepared to deal with this slim possibility.
• The chances of people having multiple positive COVID19 test results are rare, and rarer still is the likelihood that they will be one of the 500 people extracted from the thousands of daily test results to be sent to the trial team on more than one occasion. Therefore the risk of an individual being contacted twice for recruitment into PRINCIPLE is extremely low.
• NHS Digital recognises that there are likely to be more requests of this nature in future and therefore, if multiple trial require extracts of people to contact, suitable controls need to be in place within the extract process to ensure that individuals are not getting contacted for recruitment into trials more than is reasonably expected.
********************
• Request to use SCR for consented participants:
Supplementary to the requirement to receive Pillar 2 data for recruitment into PRINCIPLE, the trial team will access the Summary Care Record (SCR) of all patients recruited into the trial for the purposes of ensuring timely prescribing and safe patient care.
Currently, up to 40% of people who provide consent to participate in the PRINCIPLE Trial are delayed in starting their trial medication, or are effectively denied the opportunity to participate because of delays in checking information concerning their eligibility to safely be given the study treatments. Because so many people who are keen to contribute are being lost to the PRINCIPLE Trial, crucial study results are not yet forthcoming. If processes around ensuring timely, safe prescribing and patient care could be enhanced, then time to potentially life-saving trial results will be reduced.
The purpose of this request is therefore to seek permission for the clinical trial team, a group of dedicated doctors and nurses who are fully qualified, study-trained, accredited and registered, to review consenting patients’ Summary Care Records, in order to be able to confirm key information obtained from the patient relevant to safe patient care in the trial. Only nurses and doctors who are qualified, trained and fully registered and accredited with the General Medical Council of the UK or the Nursing and Midwifery Council of the UK who are clinical members of the PRINCIPLE Study team would review the Summary Care Record for information relevant to safe prescribing and participant care.
The Summary Care Record will be used as a timely, second check regarding medication, allergy, and co-morbidities information to support reconciliation, to ensure safe prescribing. These are all elements of a patient’s SCR with additional information which is a subset of their wider GP record. This access provides an immediate available information source to meet the need to support safe prescribing in a proportionate and timely way. In addition, the Summary Care Record will provide a further safety check, in that access to it will facilitate the opportunity for double-checking participants’ NHS Number and GP practice.
Current PRINCIPLE Trial procedures involve the clinical trial team endeavouring to identify a consenting patient’s GP, emailing or posting the participant’s consent form to the GP to obtain relevant clinical information for the study clinical team to confirm eligibility, then waiting for the GP to send selected summary clinical information from the patient’s record back to the trial clinical team, before it is then checked against patient-reported information. This proportionate access also minimises the burden on frontline general practice at a time of considerable pressures.
Access is sought only for those people who have screened eligible to be part of the Trial, and who have already signed informed consent for participation in the study and for the Trial to access their clinical records. All potential participants are asked specifically for permission for the trial team to access their medical records and have the opportunity to decline this access. In addition, they will be asked specifically and separately for permission about access to their Summary Care Record. For a patient who has provided consent to join the trial and for their SCR to be accessed, the data will be accessed by a clinician to support safe prescribing decisions immediately prior to prescribing medications. A Summary Care Record will only ever be accessed on one occasion for each individual participant/
Access is required for the period that the trial is recruiting currently this is April 20 until Sept 21.
• Access in relation the purposes of direct care:
The purpose of SCR is to allow healthcare professionals to check relevant facts prior to carrying out direct care of an individual. The clinical trial will support direct care in this use case as healthcare professionals are carrying out direct care (avoiding dangerous prescribing) for individuals, with the patient’s consent.
There will be no re-use of the data shared for direct care purposes for non-direct care purposes. but the wider context for the use of the data is as part of a clinical trial.
Note that this is a first of type access request and as an interim position it is included in the Data Sharing Agreement. This is a holding position whilst considerations are undertaken to agree whether to offer this as a service more widely to clinical trials for patient safety purposes. This allows time for an appropriate access and approval process to be developed in future, but in the meantime ensures that SCR access is recognised within the research data access process alongside the normal direct care process for access to SCR.
******************
• Request to receive 28 day follow up data (HES APC, HES Critical Care, GDPPR and Civil Registration of Deaths):
The trial follows up all consented participants for 28 days. For the just under 4,500 participants currently recruited, data for 2,000 of the participants comes from the Royal College of General Practitioners (RCGP) Research and Surveillance Centre platform, but not all GPs are registered with this system. The trial team is currently contacting GPs to collect follow up data for the other 2,000 participants, which is a huge burden on team resource and a slow process.
Due to the high rate of recruitment, the Data Safety Committee review the trial data weekly and can ask for recruitment into a trial arm to be stopped immediately. Therefore trial data needs to be made available as soon as possible so that the team can quickly issue a press statement and publication of results if required to do so. To date, there have been three trial arms stopped, essentially because all required data has not been available immediately and it has taken the team too long to collect that data and issue the information publicly. There is therefore a need to capture the required data in a more timely and efficient manner via monthly extracts from NHS Digital.
Data required is as follows:
- Did the participant attend a hospital for medical reasons between the date of randomisation and day 28 of their follow-up?
- What date did they go to hospital?
- Was this attendance likely related to COVID-19?
- If it was not likely to be related to COVID, what was the reason for the hospital visit?
- If it was COVID-19 related, did they receive oxygen while in hospital?
- Did they receive mechanical ventilation while in hospital?
- Were they admitted overnight?
- If yes, how many nights did they stay in hospital?
- Did they stay in an Intensive Care Unit during their stay in hospital?
(The above is to be sourced from the HES APC and Critical Care data).
- Was the participant prescribed any antibiotics between the date of randomisation and day 28 of their follow-up (excluding any antibiotics that may have been given as part of the study intervention)?
- If they were, what was the name of the antibiotic?
- Wat was the reason for the antibiotic prescription?
- What was the start date of antibiotic course?
(The above is to be sourced from the GDPPR data).
- Has the participant died?
- If yes, what was the date of death?
- What was the cause of death?
- Did COVID-19 contribute to death?
(The above is to be sourced from the Civil Registration of Deaths data).
Consent is in place to allow this data to be provided to the team from NHS Digital and is contained on the latest version of Patient Information Sheet on the trial website (https://www.principletrial.org/participants/participant-information-sheets):
“In addition, we will collect information from your GP records and data held by central NHS bodies (such as NHS Digital) for long-term follow-up for up to 10 years, to help us better understand the long-term effects of COVID-19 and the trial treatments.”
Only the team at the University of Oxford will access this data. No other organisations are involved in the processing or storage.
Expected output
The Principle trial will recruit to target much quicker than using current methods if the team can receive this data; the statistical team will receive follow up data in a more timely manner, therefore answering the covid-19 treatment in the community question more quickly with the aim of preventing covid-19 patients being hospitalised so reducing NHS burden.
It appears to take between 800-1200 patients per arm to answer the question for the drug of that arm. 1500 per arm is the target recruitment number, and just under 4500 patients have been recruited at the time of the second amendment to this agreement. Three arms have been closed so far, leaving two arms open. Another arm will open late February and another arm in early March, with more arms to follow thereafter.
The trial team will ensure that trial results are disseminated to all relevant parties (regular updates to the Therapeutic Taskforce, UPH committee, NIHR, DoHSC) and dissemination via media channels and to trial participants, supported by the University of Oxford. Publications will be produced as quickly as possible.
The trial is of national and international relevance during this pandemic.
DARS-NIC-411161-G4K7X-v2.5 25 February 2021 to 1 October 2021
- Title
- PRINCIPLE: Platform Randomised trial of INterventions against COVID-19 In older peoPLE
- Commercial
- No
- Sublicensing
- No
- Datasets
- 6
- Files released
- 3
Datasets: Civil Registrations of Death; COVID-19 Access to Summary Care Records; COVID-19 General Practice Extraction Service (GPES) Data for Pandemic Planning and Research (GDPPR); COVID-19 UK Non-hospital Antigen Testing Results (Pillar 2); Hospital Episode Statistics Admitted Patient Care (HES APC); Hospital Episode Statistics Critical Care (HES Critical Care)
What changed from DARS-NIC-411161-G4K7X-v1.2
Text removed is struck through; text added is underlined. Unchanged paragraphs are summarised rather than repeated.
| Field | Was | Became |
|---|---|---|
| Start date | 2021-02-25 |
Datasets: + COVID-19 General Practice Extraction Service (GPES) Data for Pandemic Planning and Research (GDPPR); + Civil Registrations of Death; + Hospital Episode Statistics Admitted Patient Care (HES APC); + Hospital Episode Statistics Critical Care (HES Critical Care)
Objective for processing
[18 paragraphs unchanged]
The trial
is currently
was initially only
recruiting via GP practices and the website and
have
had
c. 1000 participants
but need
when use of the Pillar 2 data was first proposed in in order
to rapidly increase this to 3,000 (and beyond to support further trial arms).
To achieve this, use
At the time
of the
second amendment for 28 day follow up data (while also continuing receiving
Pillar 2
testing data is proposed.
data) just under 4,5000 patients had been recruited.
The University of Oxford would like to receive names and contact details
[53 words unchanged]
trial team would like to receive data on a random cohort (initially
200)
200, now up to 500)
of people aged 50+. They may need to increase this age to
[5 words unchanged]
screen as ineligible for the trial as they lack the required comorbidities.
[4 paragraphs unchanged]
• The chances of people having multiple positive COVID19 test results are rare, and rarer still is the likelihood that they will be one of the
200
500
people extracted from the thousands of daily test results to be sent
[13 words unchanged]
an individual being contacted twice for recruitment into PRINCIPLE is extremely low.
[14 paragraphs unchanged]
******************
• Request to receive 28 day follow up data (HES APC, HES Critical Care, GDPPR and Civil Registration of Deaths):
The trial follows up all consented participants for 28 days. For the just under 4,500 participants currently recruited, data for 2,000 of the participants comes from the Royal College of General Practitioners (RCGP) Research and Surveillance Centre platform, but not all GPs are registered with this system. The trial team is currently contacting GPs to collect follow up data for the other 2,000 participants, which is a huge burden on team resource and a slow process.
Due to the high rate of recruitment, the Data Safety Committee review the trial data weekly and can ask for recruitment into a trial arm to be stopped immediately. Therefore trial data needs to be made available as soon as possible so that the team can quickly issue a press statement and publication of results if required to do so. To date, there have been three trial arms stopped, essentially because all required data has not been available immediately and it has taken the team too long to collect that data and issue the information publicly. There is therefore a need to capture the required data in a more timely and efficient manner via monthly extracts from NHS Digital.
Data required is as follows:
- Did the participant attend a hospital for medical reasons between the date of randomisation and day 28 of their follow-up?
- What date did they go to hospital?
- Was this attendance likely related to COVID-19?
- If it was not likely to be related to COVID, what was the reason for the hospital visit?
- If it was COVID-19 related, did they receive oxygen while in hospital?
- Did they receive mechanical ventilation while in hospital?
- Were they admitted overnight?
- If yes, how many nights did they stay in hospital?
- Did they stay in an Intensive Care Unit during their stay in hospital?
(The above is to be sourced from the HES APC and Critical Care data).
- Was the participant prescribed any antibiotics between the date of randomisation and day 28 of their follow-up (excluding any antibiotics that may have been given as part of the study intervention)?
- If they were, what was the name of the antibiotic?
- Wat was the reason for the antibiotic prescription?
- What was the start date of antibiotic course?
(The above is to be sourced from the GDPPR data).
- Has the participant died?
- If yes, what was the date of death?
- What was the cause of death?
- Did COVID-19 contribute to death?
(The above is to be sourced from the Civil Registration of Deaths data).
Consent is in place to allow this data to be provided to the team from NHS Digital and is contained on the latest version of Patient Information Sheet on the trial website (https://www.principletrial.org/participants/participant-information-sheets):
“In addition, we will collect information from your GP records and data held by central NHS bodies (such as NHS Digital) for long-term follow-up for up to 10 years, to help us better understand the long-term effects of COVID-19 and the trial treatments.”
Only the team at the University of Oxford will access this data. No other organisations are involved in the processing or storage.
Processing activities
[2 paragraphs unchanged]
• On a daily basis (seven days a week) NHS Digital will interrogate the Pillar 2 dataset and extract
200
up to 500
individuals at random who are 50 or over who have received a positive COVID 19 test result in the previous 24 hours.
[26 paragraphs unchanged]
**********
• Request to receive 28 day follow up data (HES APC, HES Critical Care, GDPPR and Civil Registration of Deaths):
On a monthly basis the trial team will send to NHs Digital the relevant data items for those cohort members who have hit the 28 day follow up window.
The following data items will be provided for linkage: Study ID, NHS Number, Date of Birth.
NHS Digital will link the cohort members to the aforementioned datasets and return the outputs to the team via Secure Electronic File Transfer [SEFT].
One of the data sets requested in this application (GPES Data for Pandemic Planning and Research - GDPPR) has been collected under a specific COVID-19 related direction, and as such can only be used for COVID-19 research related purposes. The COPI notice that will cover this flow of data is currently set to expire at the same time as this agreement.
Expected output
The Principle trial will recruit to target much quicker than using current methods if the team can receive this
data,
data; the statistical team will receive follow up data in a more timely manner,
therefore answering the covid-19 treatment in the community question more quickly with the aim of preventing covid-19
sufferers
patients
being hospitalised so reducing NHS burden.
The trial’s current sample size is 3000 participants which the aim is to recruit by Dec 2020.
It appears to take between 800-1200 patients per arm to answer the question for the drug of that arm. 1500 per arm is the target recruitment number, and just under 4500 patients have been recruited at the time of the second amendment to this agreement. Three arms have been closed so far, leaving two arms open. Another arm will open late February and another arm in early March, with more arms to follow thereafter.
[2 paragraphs unchanged]
Expected measurable benefits
The trial has co-primary endpoints: 1) Time taken to self-reported recovery; and
[22 words unchanged]
recovery and in reducing the incidence of hospitalisation and/or death for covid-19
sufferers.
patients.
[1 paragraph unchanged]
Target date - recruit 3000 by Dec 2020
Original target date - recruit 3,000 by Dec 2020. New target to continue recruiting beyond the 4,500 patients already recruited at time of second amendment to this agreement in March 2021.
Objective for processing
Over recent weeks, there has been an increase in the number of COVID-19 cases in the community and in hospitalisation. Currently, there are no treatments that have been proven in rigorous trials to help people with COVID-19 symptoms in the community recover quicker and reduce the need for hospital admission. It is therefore vital that the University of Oxford use this opportunity to accelerate enrolment into COVID-19 therapeutics trials.
The PRINCIPLE (Platform Randomised trial of Interventions against COVID-19 In older peoPLE) trial is the only national Urgent Public Health priority clinical trial evaluating potential therapeutics for COVID-19 in the primary care setting, endorsed by the CMOs of all four devolved nations . The trial aims to find out whether early treatment in the community speeds recovery and reduces the need for hospital admission for those with COVID-like-Illness.
PRINICIPLE is:
• Recruiting across the whole UK: anyone can participate, regardless of location.
• Light burden for both recruiters and patients; it only takes couple of minutes to complete enrolment on to the trial.
• Obtaining consent, checking eligibility, issuing study medication and materials, and follow-up is manged remotely through a central facility.
Primary objective - To assess effectiveness of trial treatments in reducing the need for hospital admission or death, for patients aged ≥50 years with comorbidity, and aged ≥65 with or without comorbidity and suspected COVID-19 infection during time of prevalent COVID-19 infections.
Secondary objectives - To explore whether trial treatment reduces
1) Duration of severe symptoms
2) Time taken to self-report recovery
3) Contacts with the health services
4) Consumption of antibiotics
5) Hospital assessment without admission
6) Oxygen administration
7) Intensive Care Unit admission
8) Mechanical ventilation
9) To determine if effects are specific to those with the infections syndrome but who test positive for COVID-19
10) Duration of hospital admission
The trial was initially only recruiting via GP practices and the website and had c. 1000 participants when use of the Pillar 2 data was first proposed in in order to rapidly increase this to 3,000 (and beyond to support further trial arms). At the time of the second amendment for 28 day follow up data (while also continuing receiving Pillar 2 data) just under 4,5000 patients had been recruited.
The University of Oxford would like to receive names and contact details (preferably a telephone number) of people who have received a positive covid-19 swab result from the Pillar 2 testing system. The trial team based in Oxford will then contact these potential participants, inform them about the trial and if they are happy, go on to screen and consent them into Principle. Daily, the trial team would like to receive data on a random cohort (initially 200, now up to 500) of people aged 50+. They may need to increase this age to 65+ if those they contact screen as ineligible for the trial as they lack the required comorbidities.
Consideration has been given to whether the trial should be contacting individuals directly, and whether the recruitment could be managed through the Test and Trace service, i.e. the service are already set up to contact individuals and could inform them of the trial when they get in touch. However, given the use of contractors to operate this service, and thereby creating an extra layer to the process, this is unlikely to fit with the timescales the trial are working to (which ties in with why they have decided to switch from GPs as the primary source of recruitment). Additionally, the trial already has a centre set up and operating remotely to manage this recruitment in a timely manner.
The question of whether ‘cold calling’ is appropriate has been considered for this application, especially against alternatives such as SMS and emailing. As time is of the essence for recruitment into PRINCIPLE, telephone is the most efficient and quickest means to ensure direct contact with the individual, who can answer questions instantly over a call. This also ensures ‘human contact’, as opposed to SMS / emails, with trained and experienced CTU research nurses working directly to the trial team providing that contact. During the calls, clear explanation will be given to individual about how the trial has been able to contact them and what to do if they do not wish to be contacted again (i.e. registering a national opt-out). The trial team will decide whether to apply the Telephone Preference Service under their own discretion. The trial team will also ensure the required comorbidities are discussed early on in the calls so as to not to get the individual’s hopes up if they are not in fact eligible for the trial. Lessons have been learned from a recent NHS Digital request for contact details provided to researchers contact people to donate blood and plasma, with careful attention paid to the various take up rates and any changes rates in these between the first and second waves of the pandemic. However, unlike that trial, PRINCIPLE could potentially be of direct benefit to the individual.
Other considerations that have been taken into account in relation to contacting individuals:
• The data relating to positive COVID19 tests is sent to NHS Digital at the same time that it is sent to the Business Services Authority, the latter process triggering the SMS to the individual informing them of their result. It then takes around four hours for the Pillar 2 dataset within NHS Digital to be updated with this information. Given that this information then needs to be extracted from the dataset at some point in the next 24 hours, then used by the trial team to make contact with the individual, the risk of the individual being informed of their test result by the trial team before they have read their SMS is small. However, the trial team should have a suitable script prepared to deal with this slim possibility.
• The chances of people having multiple positive COVID19 test results are rare, and rarer still is the likelihood that they will be one of the 500 people extracted from the thousands of daily test results to be sent to the trial team on more than one occasion. Therefore the risk of an individual being contacted twice for recruitment into PRINCIPLE is extremely low.
• NHS Digital recognises that there are likely to be more requests of this nature in future and therefore, if multiple trial require extracts of people to contact, suitable controls need to be in place within the extract process to ensure that individuals are not getting contacted for recruitment into trials more than is reasonably expected.
********************
• Request to use SCR for consented participants:
Supplementary to the requirement to receive Pillar 2 data for recruitment into PRINCIPLE, the trial team will access the Summary Care Record (SCR) of all patients recruited into the trial for the purposes of ensuring timely prescribing and safe patient care.
Currently, up to 40% of people who provide consent to participate in the PRINCIPLE Trial are delayed in starting their trial medication, or are effectively denied the opportunity to participate because of delays in checking information concerning their eligibility to safely be given the study treatments. Because so many people who are keen to contribute are being lost to the PRINCIPLE Trial, crucial study results are not yet forthcoming. If processes around ensuring timely, safe prescribing and patient care could be enhanced, then time to potentially life-saving trial results will be reduced.
The purpose of this request is therefore to seek permission for the clinical trial team, a group of dedicated doctors and nurses who are fully qualified, study-trained, accredited and registered, to review consenting patients’ Summary Care Records, in order to be able to confirm key information obtained from the patient relevant to safe patient care in the trial. Only nurses and doctors who are qualified, trained and fully registered and accredited with the General Medical Council of the UK or the Nursing and Midwifery Council of the UK who are clinical members of the PRINCIPLE Study team would review the Summary Care Record for information relevant to safe prescribing and participant care.
The Summary Care Record will be used as a timely, second check regarding medication, allergy, and co-morbidities information to support reconciliation, to ensure safe prescribing. These are all elements of a patient’s SCR with additional information which is a subset of their wider GP record. This access provides an immediate available information source to meet the need to support safe prescribing in a proportionate and timely way. In addition, the Summary Care Record will provide a further safety check, in that access to it will facilitate the opportunity for double-checking participants’ NHS Number and GP practice.
Current PRINCIPLE Trial procedures involve the clinical trial team endeavouring to identify a consenting patient’s GP, emailing or posting the participant’s consent form to the GP to obtain relevant clinical information for the study clinical team to confirm eligibility, then waiting for the GP to send selected summary clinical information from the patient’s record back to the trial clinical team, before it is then checked against patient-reported information. This proportionate access also minimises the burden on frontline general practice at a time of considerable pressures.
Access is sought only for those people who have screened eligible to be part of the Trial, and who have already signed informed consent for participation in the study and for the Trial to access their clinical records. All potential participants are asked specifically for permission for the trial team to access their medical records and have the opportunity to decline this access. In addition, they will be asked specifically and separately for permission about access to their Summary Care Record. For a patient who has provided consent to join the trial and for their SCR to be accessed, the data will be accessed by a clinician to support safe prescribing decisions immediately prior to prescribing medications. A Summary Care Record will only ever be accessed on one occasion for each individual participant/
Access is required for the period that the trial is recruiting currently this is April 20 until Sept 21.
• Access in relation the purposes of direct care:
The purpose of SCR is to allow healthcare professionals to check relevant facts prior to carrying out direct care of an individual. The clinical trial will support direct care in this use case as healthcare professionals are carrying out direct care (avoiding dangerous prescribing) for individuals, with the patient’s consent.
There will be no re-use of the data shared for direct care purposes for non-direct care purposes. but the wider context for the use of the data is as part of a clinical trial.
Note that this is a first of type access request and as an interim position it is included in the Data Sharing Agreement. This is a holding position whilst considerations are undertaken to agree whether to offer this as a service more widely to clinical trials for patient safety purposes. This allows time for an appropriate access and approval process to be developed in future, but in the meantime ensures that SCR access is recognised within the research data access process alongside the normal direct care process for access to SCR.
******************
• Request to receive 28 day follow up data (HES APC, HES Critical Care, GDPPR and Civil Registration of Deaths):
The trial follows up all consented participants for 28 days. For the just under 4,500 participants currently recruited, data for 2,000 of the participants comes from the Royal College of General Practitioners (RCGP) Research and Surveillance Centre platform, but not all GPs are registered with this system. The trial team is currently contacting GPs to collect follow up data for the other 2,000 participants, which is a huge burden on team resource and a slow process.
Due to the high rate of recruitment, the Data Safety Committee review the trial data weekly and can ask for recruitment into a trial arm to be stopped immediately. Therefore trial data needs to be made available as soon as possible so that the team can quickly issue a press statement and publication of results if required to do so. To date, there have been three trial arms stopped, essentially because all required data has not been available immediately and it has taken the team too long to collect that data and issue the information publicly. There is therefore a need to capture the required data in a more timely and efficient manner via monthly extracts from NHS Digital.
Data required is as follows:
- Did the participant attend a hospital for medical reasons between the date of randomisation and day 28 of their follow-up?
- What date did they go to hospital?
- Was this attendance likely related to COVID-19?
- If it was not likely to be related to COVID, what was the reason for the hospital visit?
- If it was COVID-19 related, did they receive oxygen while in hospital?
- Did they receive mechanical ventilation while in hospital?
- Were they admitted overnight?
- If yes, how many nights did they stay in hospital?
- Did they stay in an Intensive Care Unit during their stay in hospital?
(The above is to be sourced from the HES APC and Critical Care data).
- Was the participant prescribed any antibiotics between the date of randomisation and day 28 of their follow-up (excluding any antibiotics that may have been given as part of the study intervention)?
- If they were, what was the name of the antibiotic?
- Wat was the reason for the antibiotic prescription?
- What was the start date of antibiotic course?
(The above is to be sourced from the GDPPR data).
- Has the participant died?
- If yes, what was the date of death?
- What was the cause of death?
- Did COVID-19 contribute to death?
(The above is to be sourced from the Civil Registration of Deaths data).
Consent is in place to allow this data to be provided to the team from NHS Digital and is contained on the latest version of Patient Information Sheet on the trial website (https://www.principletrial.org/participants/participant-information-sheets):
“In addition, we will collect information from your GP records and data held by central NHS bodies (such as NHS Digital) for long-term follow-up for up to 10 years, to help us better understand the long-term effects of COVID-19 and the trial treatments.”
Only the team at the University of Oxford will access this data. No other organisations are involved in the processing or storage.
Expected output
The Principle trial will recruit to target much quicker than using current methods if the team can receive this data; the statistical team will receive follow up data in a more timely manner, therefore answering the covid-19 treatment in the community question more quickly with the aim of preventing covid-19 patients being hospitalised so reducing NHS burden.
It appears to take between 800-1200 patients per arm to answer the question for the drug of that arm. 1500 per arm is the target recruitment number, and just under 4500 patients have been recruited at the time of the second amendment to this agreement. Three arms have been closed so far, leaving two arms open. Another arm will open late February and another arm in early March, with more arms to follow thereafter.
The trial team will ensure that trial results are disseminated to all relevant parties (regular updates to the Therapeutic Taskforce, UPH committee, NIHR, DoHSC) and dissemination via media channels and to trial participants, supported by the University of Oxford. Publications will be produced as quickly as possible.
The trial is of national and international relevance during this pandemic.
DARS-NIC-411161-G4K7X-v1.2 1 December 2020 to 1 October 2021
- Title
- PRINCIPLE: Platform Randomised trial of INterventions against COVID-19 In older peoPLE
- Commercial
- No
- Sublicensing
- No
- Datasets
- 2
- Files released
- 29
Datasets: COVID-19 Access to Summary Care Records; COVID-19 UK Non-hospital Antigen Testing Results (Pillar 2)
What changed from DARS-NIC-411161-G4K7X-v0.2
Text removed is struck through; text added is underlined. Unchanged paragraphs are summarised rather than repeated.
| Field | Was | Became |
|---|---|---|
| Start date | 2020-12-01 | |
| End date | 2021-10-01 |
Datasets: + COVID-19 Access to Summary Care Records
Objective for processing
[21 paragraphs unchanged]
The question of whether ‘cold calling’ is appropriate has been considered for
[131 words unchanged]
required comorbidities are discussed early on in the calls so as to
bot
not
to get the individual’s hopes up if they are not in fact
[54 words unchanged]
that trial, PRINCIPLE could potentially be of direct benefit to the individual.
[4 paragraphs unchanged]
********************
• Request to use SCR for consented participants:
Supplementary to the requirement to receive Pillar 2 data for recruitment into PRINCIPLE, the trial team will access the Summary Care Record (SCR) of all patients recruited into the trial for the purposes of ensuring timely prescribing and safe patient care.
Currently, up to 40% of people who provide consent to participate in the PRINCIPLE Trial are delayed in starting their trial medication, or are effectively denied the opportunity to participate because of delays in checking information concerning their eligibility to safely be given the study treatments. Because so many people who are keen to contribute are being lost to the PRINCIPLE Trial, crucial study results are not yet forthcoming. If processes around ensuring timely, safe prescribing and patient care could be enhanced, then time to potentially life-saving trial results will be reduced.
The purpose of this request is therefore to seek permission for the clinical trial team, a group of dedicated doctors and nurses who are fully qualified, study-trained, accredited and registered, to review consenting patients’ Summary Care Records, in order to be able to confirm key information obtained from the patient relevant to safe patient care in the trial. Only nurses and doctors who are qualified, trained and fully registered and accredited with the General Medical Council of the UK or the Nursing and Midwifery Council of the UK who are clinical members of the PRINCIPLE Study team would review the Summary Care Record for information relevant to safe prescribing and participant care.
The Summary Care Record will be used as a timely, second check regarding medication, allergy, and co-morbidities information to support reconciliation, to ensure safe prescribing. These are all elements of a patient’s SCR with additional information which is a subset of their wider GP record. This access provides an immediate available information source to meet the need to support safe prescribing in a proportionate and timely way. In addition, the Summary Care Record will provide a further safety check, in that access to it will facilitate the opportunity for double-checking participants’ NHS Number and GP practice.
Current PRINCIPLE Trial procedures involve the clinical trial team endeavouring to identify a consenting patient’s GP, emailing or posting the participant’s consent form to the GP to obtain relevant clinical information for the study clinical team to confirm eligibility, then waiting for the GP to send selected summary clinical information from the patient’s record back to the trial clinical team, before it is then checked against patient-reported information. This proportionate access also minimises the burden on frontline general practice at a time of considerable pressures.
Access is sought only for those people who have screened eligible to be part of the Trial, and who have already signed informed consent for participation in the study and for the Trial to access their clinical records. All potential participants are asked specifically for permission for the trial team to access their medical records and have the opportunity to decline this access. In addition, they will be asked specifically and separately for permission about access to their Summary Care Record. For a patient who has provided consent to join the trial and for their SCR to be accessed, the data will be accessed by a clinician to support safe prescribing decisions immediately prior to prescribing medications. A Summary Care Record will only ever be accessed on one occasion for each individual participant/
Access is required for the period that the trial is recruiting currently this is April 20 until Sept 21.
• Access in relation the purposes of direct care:
The purpose of SCR is to allow healthcare professionals to check relevant facts prior to carrying out direct care of an individual. The clinical trial will support direct care in this use case as healthcare professionals are carrying out direct care (avoiding dangerous prescribing) for individuals, with the patient’s consent.
There will be no re-use of the data shared for direct care purposes for non-direct care purposes. but the wider context for the use of the data is as part of a clinical trial.
Note that this is a first of type access request and as an interim position it is included in the Data Sharing Agreement. This is a holding position whilst considerations are undertaken to agree whether to offer this as a service more widely to clinical trials for patient safety purposes. This allows time for an appropriate access and approval process to be developed in future, but in the meantime ensures that SCR access is recognised within the research data access process alongside the normal direct care process for access to SCR.
Processing activities
[12 paragraphs unchanged] ******************** • Request to use SCR for consented participants: As per section 5A, once participants are recruited into PRINCIPLE, the trial team will access their Summary Care Record. This will be through ‘SCR Core’ or ‘SCR Additional Information’, depending on what is available for each participant. SCR Core includes: • current medication • allergies and details of any previous bad reactions to medicines • the name, address, date of birth and NHS number of the patient SCR Addition Information includes: • significant medical history (past and present) • reason for medication • anticipatory care information (such as information about the management of long term conditions) • end of life care information (from the SCCI1580 national dataset) • immunisations. Data is minimised as access is only for the consented cohort for the trial. The Clinical trial team will use SCRa and build on best practice by identifying the patient’s NHS number after a demographic search and using this to confirm the patient’s identity as well as ensuring the NHS Number is noted on any paperwork being returned to the patient’s practice regarding their participation in the trial. The SCR Team at NHS Digital will create a new position for the trial team which allows access to SCR via SCRa/Spine Portal and does not include emergency access. SCR access is time limited for the duration of the trial; this will be achieved with the use of roles to be applied to smartcards to be time limited for the duration of the trial. The trial team will not retain information obtained from SCR once the eligibility checks have been done: they will record that the SCR has been accessed, and the audit trail within the SCR will also log who has accessed the record.
Benefits reported
Stated in the previous version and removed here.
Yielded Benefits is not a requirement for new applications.
Unchanged: Expected output, Expected measurable benefits.
Objective for processing
Over recent weeks, there has been an increase in the number of COVID-19 cases in the community and in hospitalisation. Currently, there are no treatments that have been proven in rigorous trials to help people with COVID-19 symptoms in the community recover quicker and reduce the need for hospital admission. It is therefore vital that the University of Oxford use this opportunity to accelerate enrolment into COVID-19 therapeutics trials.
The PRINCIPLE (Platform Randomised trial of Interventions against COVID-19 In older peoPLE) trial is the only national Urgent Public Health priority clinical trial evaluating potential therapeutics for COVID-19 in the primary care setting, endorsed by the CMOs of all four devolved nations . The trial aims to find out whether early treatment in the community speeds recovery and reduces the need for hospital admission for those with COVID-like-Illness.
PRINICIPLE is:
• Recruiting across the whole UK: anyone can participate, regardless of location.
• Light burden for both recruiters and patients; it only takes couple of minutes to complete enrolment on to the trial.
• Obtaining consent, checking eligibility, issuing study medication and materials, and follow-up is manged remotely through a central facility.
Primary objective - To assess effectiveness of trial treatments in reducing the need for hospital admission or death, for patients aged ≥50 years with comorbidity, and aged ≥65 with or without comorbidity and suspected COVID-19 infection during time of prevalent COVID-19 infections.
Secondary objectives - To explore whether trial treatment reduces
1) Duration of severe symptoms
2) Time taken to self-report recovery
3) Contacts with the health services
4) Consumption of antibiotics
5) Hospital assessment without admission
6) Oxygen administration
7) Intensive Care Unit admission
8) Mechanical ventilation
9) To determine if effects are specific to those with the infections syndrome but who test positive for COVID-19
10) Duration of hospital admission
The trial is currently recruiting via GP practices and the website and have c. 1000 participants but need to rapidly increase this to 3,000 (and beyond to support further trial arms). To achieve this, use of the Pillar 2 testing data is proposed.
The University of Oxford would like to receive names and contact details (preferably a telephone number) of people who have received a positive covid-19 swab result from the Pillar 2 testing system. The trial team based in Oxford will then contact these potential participants, inform them about the trial and if they are happy, go on to screen and consent them into Principle. Daily, the trial team would like to receive data on a random cohort (initially 200) of people aged 50+. They may need to increase this age to 65+ if those they contact screen as ineligible for the trial as they lack the required comorbidities.
Consideration has been given to whether the trial should be contacting individuals directly, and whether the recruitment could be managed through the Test and Trace service, i.e. the service are already set up to contact individuals and could inform them of the trial when they get in touch. However, given the use of contractors to operate this service, and thereby creating an extra layer to the process, this is unlikely to fit with the timescales the trial are working to (which ties in with why they have decided to switch from GPs as the primary source of recruitment). Additionally, the trial already has a centre set up and operating remotely to manage this recruitment in a timely manner.
The question of whether ‘cold calling’ is appropriate has been considered for this application, especially against alternatives such as SMS and emailing. As time is of the essence for recruitment into PRINCIPLE, telephone is the most efficient and quickest means to ensure direct contact with the individual, who can answer questions instantly over a call. This also ensures ‘human contact’, as opposed to SMS / emails, with trained and experienced CTU research nurses working directly to the trial team providing that contact. During the calls, clear explanation will be given to individual about how the trial has been able to contact them and what to do if they do not wish to be contacted again (i.e. registering a national opt-out). The trial team will decide whether to apply the Telephone Preference Service under their own discretion. The trial team will also ensure the required comorbidities are discussed early on in the calls so as to not to get the individual’s hopes up if they are not in fact eligible for the trial. Lessons have been learned from a recent NHS Digital request for contact details provided to researchers contact people to donate blood and plasma, with careful attention paid to the various take up rates and any changes rates in these between the first and second waves of the pandemic. However, unlike that trial, PRINCIPLE could potentially be of direct benefit to the individual.
Other considerations that have been taken into account in relation to contacting individuals:
• The data relating to positive COVID19 tests is sent to NHS Digital at the same time that it is sent to the Business Services Authority, the latter process triggering the SMS to the individual informing them of their result. It then takes around four hours for the Pillar 2 dataset within NHS Digital to be updated with this information. Given that this information then needs to be extracted from the dataset at some point in the next 24 hours, then used by the trial team to make contact with the individual, the risk of the individual being informed of their test result by the trial team before they have read their SMS is small. However, the trial team should have a suitable script prepared to deal with this slim possibility.
• The chances of people having multiple positive COVID19 test results are rare, and rarer still is the likelihood that they will be one of the 200 people extracted from the thousands of daily test results to be sent to the trial team on more than one occasion. Therefore the risk of an individual being contacted twice for recruitment into PRINCIPLE is extremely low.
• NHS Digital recognises that there are likely to be more requests of this nature in future and therefore, if multiple trial require extracts of people to contact, suitable controls need to be in place within the extract process to ensure that individuals are not getting contacted for recruitment into trials more than is reasonably expected.
********************
• Request to use SCR for consented participants:
Supplementary to the requirement to receive Pillar 2 data for recruitment into PRINCIPLE, the trial team will access the Summary Care Record (SCR) of all patients recruited into the trial for the purposes of ensuring timely prescribing and safe patient care.
Currently, up to 40% of people who provide consent to participate in the PRINCIPLE Trial are delayed in starting their trial medication, or are effectively denied the opportunity to participate because of delays in checking information concerning their eligibility to safely be given the study treatments. Because so many people who are keen to contribute are being lost to the PRINCIPLE Trial, crucial study results are not yet forthcoming. If processes around ensuring timely, safe prescribing and patient care could be enhanced, then time to potentially life-saving trial results will be reduced.
The purpose of this request is therefore to seek permission for the clinical trial team, a group of dedicated doctors and nurses who are fully qualified, study-trained, accredited and registered, to review consenting patients’ Summary Care Records, in order to be able to confirm key information obtained from the patient relevant to safe patient care in the trial. Only nurses and doctors who are qualified, trained and fully registered and accredited with the General Medical Council of the UK or the Nursing and Midwifery Council of the UK who are clinical members of the PRINCIPLE Study team would review the Summary Care Record for information relevant to safe prescribing and participant care.
The Summary Care Record will be used as a timely, second check regarding medication, allergy, and co-morbidities information to support reconciliation, to ensure safe prescribing. These are all elements of a patient’s SCR with additional information which is a subset of their wider GP record. This access provides an immediate available information source to meet the need to support safe prescribing in a proportionate and timely way. In addition, the Summary Care Record will provide a further safety check, in that access to it will facilitate the opportunity for double-checking participants’ NHS Number and GP practice.
Current PRINCIPLE Trial procedures involve the clinical trial team endeavouring to identify a consenting patient’s GP, emailing or posting the participant’s consent form to the GP to obtain relevant clinical information for the study clinical team to confirm eligibility, then waiting for the GP to send selected summary clinical information from the patient’s record back to the trial clinical team, before it is then checked against patient-reported information. This proportionate access also minimises the burden on frontline general practice at a time of considerable pressures.
Access is sought only for those people who have screened eligible to be part of the Trial, and who have already signed informed consent for participation in the study and for the Trial to access their clinical records. All potential participants are asked specifically for permission for the trial team to access their medical records and have the opportunity to decline this access. In addition, they will be asked specifically and separately for permission about access to their Summary Care Record. For a patient who has provided consent to join the trial and for their SCR to be accessed, the data will be accessed by a clinician to support safe prescribing decisions immediately prior to prescribing medications. A Summary Care Record will only ever be accessed on one occasion for each individual participant/
Access is required for the period that the trial is recruiting currently this is April 20 until Sept 21.
• Access in relation the purposes of direct care:
The purpose of SCR is to allow healthcare professionals to check relevant facts prior to carrying out direct care of an individual. The clinical trial will support direct care in this use case as healthcare professionals are carrying out direct care (avoiding dangerous prescribing) for individuals, with the patient’s consent.
There will be no re-use of the data shared for direct care purposes for non-direct care purposes. but the wider context for the use of the data is as part of a clinical trial.
Note that this is a first of type access request and as an interim position it is included in the Data Sharing Agreement. This is a holding position whilst considerations are undertaken to agree whether to offer this as a service more widely to clinical trials for patient safety purposes. This allows time for an appropriate access and approval process to be developed in future, but in the meantime ensures that SCR access is recognised within the research data access process alongside the normal direct care process for access to SCR.
Expected output
The Principle trial will recruit to target much quicker than using current methods if the team can receive this data, therefore answering the covid-19 treatment in the community question more quickly with the aim of preventing covid-19 sufferers being hospitalised so reducing NHS burden.
The trial’s current sample size is 3000 participants which the aim is to recruit by Dec 2020.
The trial team will ensure that trial results are disseminated to all relevant parties (regular updates to the Therapeutic Taskforce, UPH committee, NIHR, DoHSC) and dissemination via media channels and to trial participants, supported by the University of Oxford. Publications will be produced as quickly as possible.
The trial is of national and international relevance during this pandemic.
DARS-NIC-411161-G4K7X-v0.2 5 November 2020 to 4 May 2021
- Title
- PRINCIPLE: Platform Randomised trial of INterventions against COVID-19 In older peoPLE
- Commercial
- No
- Sublicensing
- No
- Datasets
- 1
- Files released
- 21
Datasets: COVID-19 UK Non-hospital Antigen Testing Results (Pillar 2)
Objective for processing
Over recent weeks, there has been an increase in the number of COVID-19 cases in the community and in hospitalisation. Currently, there are no treatments that have been proven in rigorous trials to help people with COVID-19 symptoms in the community recover quicker and reduce the need for hospital admission. It is therefore vital that the University of Oxford use this opportunity to accelerate enrolment into COVID-19 therapeutics trials.
The PRINCIPLE (Platform Randomised trial of Interventions against COVID-19 In older peoPLE) trial is the only national Urgent Public Health priority clinical trial evaluating potential therapeutics for COVID-19 in the primary care setting, endorsed by the CMOs of all four devolved nations . The trial aims to find out whether early treatment in the community speeds recovery and reduces the need for hospital admission for those with COVID-like-Illness.
PRINICIPLE is:
• Recruiting across the whole UK: anyone can participate, regardless of location.
• Light burden for both recruiters and patients; it only takes couple of minutes to complete enrolment on to the trial.
• Obtaining consent, checking eligibility, issuing study medication and materials, and follow-up is manged remotely through a central facility.
Primary objective - To assess effectiveness of trial treatments in reducing the need for hospital admission or death, for patients aged ≥50 years with comorbidity, and aged ≥65 with or without comorbidity and suspected COVID-19 infection during time of prevalent COVID-19 infections.
Secondary objectives - To explore whether trial treatment reduces
1) Duration of severe symptoms
2) Time taken to self-report recovery
3) Contacts with the health services
4) Consumption of antibiotics
5) Hospital assessment without admission
6) Oxygen administration
7) Intensive Care Unit admission
8) Mechanical ventilation
9) To determine if effects are specific to those with the infections syndrome but who test positive for COVID-19
10) Duration of hospital admission
The trial is currently recruiting via GP practices and the website and have c. 1000 participants but need to rapidly increase this to 3,000 (and beyond to support further trial arms). To achieve this, use of the Pillar 2 testing data is proposed.
The University of Oxford would like to receive names and contact details (preferably a telephone number) of people who have received a positive covid-19 swab result from the Pillar 2 testing system. The trial team based in Oxford will then contact these potential participants, inform them about the trial and if they are happy, go on to screen and consent them into Principle. Daily, the trial team would like to receive data on a random cohort (initially 200) of people aged 50+. They may need to increase this age to 65+ if those they contact screen as ineligible for the trial as they lack the required comorbidities.
Consideration has been given to whether the trial should be contacting individuals directly, and whether the recruitment could be managed through the Test and Trace service, i.e. the service are already set up to contact individuals and could inform them of the trial when they get in touch. However, given the use of contractors to operate this service, and thereby creating an extra layer to the process, this is unlikely to fit with the timescales the trial are working to (which ties in with why they have decided to switch from GPs as the primary source of recruitment). Additionally, the trial already has a centre set up and operating remotely to manage this recruitment in a timely manner.
The question of whether ‘cold calling’ is appropriate has been considered for this application, especially against alternatives such as SMS and emailing. As time is of the essence for recruitment into PRINCIPLE, telephone is the most efficient and quickest means to ensure direct contact with the individual, who can answer questions instantly over a call. This also ensures ‘human contact’, as opposed to SMS / emails, with trained and experienced CTU research nurses working directly to the trial team providing that contact. During the calls, clear explanation will be given to individual about how the trial has been able to contact them and what to do if they do not wish to be contacted again (i.e. registering a national opt-out). The trial team will decide whether to apply the Telephone Preference Service under their own discretion. The trial team will also ensure the required comorbidities are discussed early on in the calls so as to bot to get the individual’s hopes up if they are not in fact eligible for the trial. Lessons have been learned from a recent NHS Digital request for contact details provided to researchers contact people to donate blood and plasma, with careful attention paid to the various take up rates and any changes rates in these between the first and second waves of the pandemic. However, unlike that trial, PRINCIPLE could potentially be of direct benefit to the individual.
Other considerations that have been taken into account in relation to contacting individuals:
• The data relating to positive COVID19 tests is sent to NHS Digital at the same time that it is sent to the Business Services Authority, the latter process triggering the SMS to the individual informing them of their result. It then takes around four hours for the Pillar 2 dataset within NHS Digital to be updated with this information. Given that this information then needs to be extracted from the dataset at some point in the next 24 hours, then used by the trial team to make contact with the individual, the risk of the individual being informed of their test result by the trial team before they have read their SMS is small. However, the trial team should have a suitable script prepared to deal with this slim possibility.
• The chances of people having multiple positive COVID19 test results are rare, and rarer still is the likelihood that they will be one of the 200 people extracted from the thousands of daily test results to be sent to the trial team on more than one occasion. Therefore the risk of an individual being contacted twice for recruitment into PRINCIPLE is extremely low.
• NHS Digital recognises that there are likely to be more requests of this nature in future and therefore, if multiple trial require extracts of people to contact, suitable controls need to be in place within the extract process to ensure that individuals are not getting contacted for recruitment into trials more than is reasonably expected.
Expected output
The Principle trial will recruit to target much quicker than using current methods if the team can receive this data, therefore answering the covid-19 treatment in the community question more quickly with the aim of preventing covid-19 sufferers being hospitalised so reducing NHS burden.
The trial’s current sample size is 3000 participants which the aim is to recruit by Dec 2020.
The trial team will ensure that trial results are disseminated to all relevant parties (regular updates to the Therapeutic Taskforce, UPH committee, NIHR, DoHSC) and dissemination via media channels and to trial participants, supported by the University of Oxford. Publications will be produced as quickly as possible.
The trial is of national and international relevance during this pandemic.
Benefits reported
Yielded Benefits is not a requirement for new applications.
Register history
When this agreement appeared in, or was edited in, each monthly edition of the register. Built by comparing every edition this site holds, the earliest of which is July 2021.
-
July 2021 —
already listed in the earliest edition this site holds, so it may be older. 4 versions: DARS-NIC-411161-G4K7X-v0.2, DARS-NIC-411161-G4K7X-v1.2, DARS-NIC-411161-G4K7X-v2.5, DARS-NIC-411161-G4K7X-v3.2
-
November 2021
1 version added: DARS-NIC-411161-G4K7X-v4.4
-
May 2022
1 version added: DARS-NIC-411161-G4K7X-v5.4
Cite this page
NHS England (2026) Data Uses Register, September 2026 edition, agreement DARS-NIC-411161-G4K7X, “PRINCIPLE: Platform Randomised Trial of Treatments in the Community for Epidemic and Pandemic Illnesses”. Read via NHS Data Access Explorer (unofficial), https://healthdatauses.uk/agreements/dars-nic-411161-g4k7x/ (accessed [date]).
This address stays the same, but the page is rebuilt with each monthly edition, so the citation names the edition it shows. Every edition's data is kept in the facts store.
Source: datausesregister_september2026.xlsx, September 2026 edition of the NHS England Data Uses Register. Search that workbook for DARS-NIC-411161-G4K7X to see the original rows.