COVID-positive adults for FLARE trial

The purpose of this application is to identify individuals who have recently been diagnosed with COVID-19 via the national testing programme. These individuals will be telephoned by the trial team at the Royal Free London NHS Foundation Trust to tell them about the FLARE clinical trial and invite them to enrol. The aim is to make eligible subjects aware of the FLARE clinical trial and give them an opportunity to join a study testing treatments for COVID-19.

The FLARE trial is investigating two antiviral drugs (favipiravir and lopinavir/ritonavir) for early COVID-19 disease. Favipiravir has demonstrated good in vitro activity against SARS-CoV-2, the causative virus of COVID-19, and early clinical data have been encouraging. Lopinavir/ritonavir also has reasonable activity against the virus and may synergise with favipiravir so that the combination is particularly effective. By treating people with effective antivirals early in the disease, the aim is to interrupt viral replication thereby shortening the duration of symptoms and reducing risk of complications.

The study is a Phase II, randomised, double-blind, placebo-controlled trial with a factorial design. It will provide robust data on the effectiveness of the treatments on the level of the virus (viral load) in the participants’ saliva as well as data on safety and tolerability. Additional secondary end-points include the effect of therapy on duration of fever, hospitalisation, and the extent of mutation in the SARS-CoV-2 virus.

Further information about the FLARE clinical trial can be found here: https://clinicaltrials.gov/ct2/show/NCT04499677

The trial is currently recruiting through hospital (A&E) attendees at Royal Free London and Occupational Health departments and has under 50 people recruited. Given that the trial aims to recruit 240 participants, and the recruitment period will end on 31st March 2021, use of the PiIlar 2 data to speed up the recruitment process is proposed.

The FLARE clinical trial’s use of the Pillar 2 data is permitted under Regulation 3(3) of COPI. The confidential patient information to be processed is required for a COVID-19 purpose and will be processed solely for that COVID-19 purpose in accordance with Regulation 7 of COPI.

By receiving lists of potentially eligible individuals from the Pillar 2 dataset who have recently been diagnosed with COVID-19, the trial team will be able to recruit willing individuals onto the FLARE trial, and at greater speed than previously, and therefore enable crucial research evaluating COVID-19 treatments. Recruitment onto FLARE is the only purpose for the trial team receiving this data and no more Pillar 2 data will be required after the target of 240 participants is reached.

The data subjects will be adults age 18-70 years, living in London, with a positive COVID-19 test in the last 7 days. By restricting the geographical spread of the data to London, the aim is that the majority of those contacted would be living in an area which is suitable for trial enrolment due to the location of the trial site, Royal Free London.

The minimum data required for making contact with potential trial participants is:

- Name of the subject: needed to identify that the trial team are speaking to the correct person on the phone.

- Telephone number: needed in order to contact the subjects.

- Postcode within London: needed to choose who to contact, as priority will be given to those individuals living close to the trial site (Royal Free Hospital).

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.

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 FLARE, 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 research nurses working directly for the trial team providing that contact. During the calls, clear explanation will be given to individuals 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 should apply the Telephone Preference Service when contacting individuals s as a proxy in the absence of a more sophisticated means of ascertaining people who might not want to be contacted by telephone. The trial team will also ensure any eligibility considerations 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 to contact people to donate blood and plasma, with careful attention paid to the various take up rates and any changes to these rates between the first and second waves of the pandemic. However, unlike that trial, FLARE 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 300 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 FLARE 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.

There will be no flow of data into NHS Digital as part of this application. The data will be accessed by the FLARE clinical trial team in order to contact the data subjects and will not be used beyond this. The data will be processed at the Royal Free Hospital and not passed on beyond the FLARE clinical trial team.

The location, name and telephone number of the data subjects will be used to contact them and invite them to join the clinical trial. This is the sole use of the data. The data will not be linked to any other data. The data will be accessed on NHS computers on the Royal Free network which is a secure environment.

A detailed breakdown of the data processing is as follows:

• Twice a week, and for a two week period, NHS Digital will interrogate the Pillar 2 dataset and extract 300 individuals at random who are aged between 18 and 70 years, live in certain postcode areas of London, and who have received a positive COVID 19 test result in the previous 24 hours. If less than 300 records are extracted, all of these will be provided.

• The individuals will be resident in England-only as determined by the postcodes of residence.

• 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.

• Individuals who have signed up for the Telephone Preference Service will need to be taken into account.

• The flow from NHS Digital to the trial team will be via a SEFT account.

• The trial team will use the data provided to make outbound telephone calls to ask if the individuals would be interested in being recruited into the trial.

• The aim is to contact 300 people following each drop of data and recruit as many as possible into the trial.

• The number of individual contact details supplied by NHS Digital to the trial team in each drop may be reviewed once the take-up rate is better understood.

• Additionally, the original two week time period, plus the number of extracts / drops per week may be reviewed and amended once the take-up rate is better understood.

• The trial team will hold the data securely adhering to all IG Policies in the Dept., the team will call the data subjects 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.

Royal Free London NHS Foundation Trust and University College London are joint Data Controllers for the data, with Royal Free London NHS Foundation Trust also acting as the sole Data Processor. Although University College London have delegated responsibility for recruitment to the Royal Free London NHS Foundation Trust, they retain responsibilities for the way in which the trial is run and the trial documentation and therefore have overall responsibilities as a Data Controller.

No other bodies or organisations (including other bases within Royal Free London) need to be included as Data Controllers or Data Processors in this agreement.

LifeArc are the charity funder of the FLARE trial. Note that the funder will not have influence on the design or outcomes of the trial, nor suppress any of the findings of the research.

The data will be used to identify individuals who are likely to be eligible to enrol in the FLARE clinical trial due to their recent positive COVID-19 swab, age and location. Their names and telephone numbers will be used in order to call them and invite them to enrol on the trial. If they consent to being enrolled on the trial, then all subsequent data will be collected as needed from the individuals directly with informed consent as per the study protocol and will be subject to the FLARE clinical trial approved procedures, privacy agreements, data agreements, etc.

As previously described, there will be no direct outputs from the data which is covered in this application. The data asked for will be used only to identify individuals to invite them to enrol in the FLARE clinical trial.

There will be no dissemination or communication of the data from this application. The FLARE clinical trial itself will generate outputs which will be communicated and disseminated; however, the data from this application is only going to be used to identify individuals so they can be invited to enrol on the clinical trial.

There are no outputs from the data itself. However, the FLARE clinical trial aims to complete enrolment by 31st March 2021 with outputs in the following months in 2021.

As previously described, there will be no dissemination of the data from this application. However, the data will be used to invite subjects to enrol on the FLARE clinical trial. This trial will benefit health care by identifying effective antiviral treatments for COVID-19.

As previously described, there will be no dissemination of the data from this application. However, the global coronavirus pandemic is an unprecedented health crisis and to date there are no proven treatments for early COVID-19 disease. The data from this application will play a crucial role in finding individuals who are willing to take promising experimental treatments for COVID-19 and ultimately help to identify effective treatments.

As previously described, there will be no direct outputs from the data. However, the data will be used to invite subjects to enrol on the FLARE clinical trial. This trial will benefit health care by evaluating antiviral treatments for COVID-19 which are urgently needed.

Not stated in the register.