A phase I study to determine safety and immunogenicity of the candidate COVID-19 vaccine AZD1222 delivered by aerosol in healthy adult volunteers (COVAXAER01)

This Data Sharing Agreement authorises the use of information voluntarily provided to NHS England by individuals who have given permission to be contacted about potential participation in COVID-19 vaccine clinical trials. The data will be processed on behalf of the Data Controller, Imperial College London, by NHS England as a Data Processor for the purpose of supporting recruitment to participate in a COVID-19 vaccine trial being run by Imperial College London

The following provides background to the Permission to Contact (PtC) Service:

NHS England has agreed to work in partnership with the National Institute of Health Research (NIHR) to build and host a first of type online Permission to Contact Service on nhs.uk where members of the public can register their details and give their permission to be contacted by researchers working on NIHR approved UK coronavirus vaccine trials about participating in those trials. This PtC Service, which is called “Sign Up to be Contacted about Coronavirus Vaccine Studies” on the nhs.uk website was launched as a national service on 20th July 2020.

This Service enables participants to:

• Provide permission for NHS England to share an individual’s details provided through the Service with the researchers undertaking COVID-19 UK vaccine trials for the purposes of researchers contacting that individual about taking part in those trials.

• Provide their permission to be contacted by NHS England about progress and outcomes from CV19 vaccine studies and in relation to the development of the PtC Service, including to inform them of opportunities to participate in other types of health research.

The data collected from individuals who sign up includes sufficient information to achieve the following purposes:

• Matching potentially eligible participants to eligibility criteria provided by the vaccine trials for their specific studies. This data will comprise of age, sex, geographic locations, type of employment, and a number health question e.g. about whether they have long-term health conditions.

• Providing relevant details of potentially eligible participants which have been obtained through the Service to researchers. This will allow the researchers to contact the participants with a view to discussing their taking part in a trial and if so, to obtain their further permission to take part in the trial.

• NHS England will provide access to the information obtained from individuals through the Service via the existing Data Access Request Service (DARS) process available to researchers working on UK COVID-19 vaccine trials sponsored by the National Institute of Health Research. The Service will only provide researchers with the data collected directly from individuals themselves through the Service.

The contact details will be used to invite potentially eligible individuals to undertake an eligibility assessment and, if eligible, to give informed consent to participate in this trial. NHS England, as Data Processor acting on behalf of Imperial College London, will be sending the communication to eligible participants.

This request relates specifically to a vaccine trial. The full title for this study is: A phase I study to determine safety and immunogenicity of the candidate COVID-19 vaccine AZD1222 delivered by aerosol in healthy adult volunteers (COVAXAER01)

The COVAXER01 phase I study will test the COVID-19 vaccine candidate AZD1222 (produced by AstraZeneca) to investigate its safety, tolerability and capability of boosting immune responses both in the blood and the lung when administered to the respiratory tract in volunteers previously vaccinated by intramuscular COVID-19 vaccination. Using standardised methods, the study team will measure immune responses in the blood, nose and lower airway and compare with data from ongoing clinical trials of intramuscular vaccination. By doing this analysis, the study team aim to demonstrate the effect of the delivery method and provide the critical information required to begin further clinical trials to show the efficacy of this needle-free vaccination strategy for booster vaccination. Recruitment will take place in a step wise manner to ensure volunteers safety. The first volunteer will receive the lowest dose of vaccine and then providing there are no safety concerns after Day 1, Day 3 and Day 7 follow up visits, a further two more volunteers will be invited to receive the lowest dose of vaccine and assessed after Day 1, Day 3 and Day 7 for any side effects. The safety profile will then be assessed by a Data Safety Monitoring Board (DSMB) before escalating to the next dose cohort. This will then be repeated (if no safety concerns) for the medium and high dose of vaccine, until the target recruitment of volunteers is reached.

The aim of this agreement is to recruit a total of 27 participants.

The GDPR legal basis for processing the data is GDPR Article 6 (1) (e). Processing is carried out by a public organisation in the public interest, in order to understand the safety, tolerability and capability of boosting immune responses using the above-stated vaccine candidate and thus potentially helping to protest the UK patient population in the future.

In addition to the above GDPR Legal Basis for Processing, this agreement refers to health data, which is a Special Category of Personal Data and therefore Imperial College London also relies upon Article 9(2)(j) (processing is necessary for archiving purposes in the public interest, scientific or historical research purposes or statistical purposes in accordance with Article 89(1) based on Union or Member State law which shall be proportionate to the aim pursued, respect the essence of the right to data protection and provide for suitable and specific measures to safeguard the fundamental rights and the interests of the data subject). NHS England is content that the purpose of this study is the use of information voluntarily provided to NHS England by individuals who have given permission to be contacted about potential participation in COVID-19 vaccine clinical trials, thus clearly demonstrating that the study purpose is research into public health and therefore providing benefit to health and social care in the UK.

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. The ways in which the processing of data will be of benefit to the public – thereby demonstrating that the processing is in the public interest – are described in section ‘5d. ii. Expected Measurable Benefits to Health and/or Social Care Including Target Date’.

- In accordance with GDPR Article 89(1) processing is subject to appropriate safeguards. These include:

i. The data recipient’s technical and organisational measures to safeguard the data have been assessed and meet NHS England's acceptance criteria (see sections 2 and 5b of this application for further details) although it should be noted that Imperial College London is not receiving data from NHS England in this agreement;

ii. The requested data has been assessed as proportionate to the aim pursued (see section 5a of this application for further details);

iii. Controls, data retention and processing activities have been assessed to ensure respect to the essence of the right to data protection;

iv. Measures to protect the rights and freedoms of data subjects have been assessed including transparency (fair processing) publishing subject’s rights.

NHS England is content that the purpose of this study is the use of information voluntarily provided to NHS England by individuals who have given permission to be contacted about potential participation in COVID-19 vaccine clinical trials, thus clearly demonstrating that the study purpose is research into public health and therefore providing benefit to health and social care in the UK.

In the interests of full transparency, it is noted here that AstraZeneca has supplied the AZD1222 vaccine free of charge to Imperial College London for use in this trial. The data will be used in support of the development of a commercial vaccine(s) that, should the research prove successful, will generate income for the commercial companies involved, to cover the development costs of the vaccine and also generate profit for that organisation.

AstraZeneca will not have any access to NHS England record-level data. AstraZeneca do not make any decisions about the means by which any personal data is being processed for this study and therefore they are not considered a data controller in this agreement.

NHS England will extract a list of patients meeting the following criteria, where that criteria can be ascertained using the NHS England COVID-19 Vaccine Research Registry:

Personal Information:

Age

Location

Sex at birth

Ethnic Group

Health questions:

Flu Jab

Diabetes

Asthma

Lung conditions

Liver conditions

Heart conditions

Cancer treatment

Bleeding disorders

Immune system disorders

NHS England will identify all individuals within the PtC dataset meeting the relevant criteria and will extract their names, date of birth, email addresses and postcodes.

It is not known in advance how many individuals meeting the above criteria will have records in the PtC dataset. The number may be amended, and the process may be repeated depending on the level of response. In the event of the trial not achieving a suitable balance in recruited participants, subsequent mail outs may restrict the required criteria to a greater degree than previously. This could encompass any part of the criteria, such as age, gender, ethnicity or location and various others, depending on how the recruitment progresses.

NHS England will write to the individuals in the subset inviting them to participate within the trial using ethically approved text provided by Imperial College London. The email will remind the individuals of the background of the permission to contact programme and give them the opportunity to state that they do not wish to be contacted again. The email will also direct volunteers to NIHR’s Be Part of Research website to access study information and regional contact information. Individuals will not be contacted multiple times under this Agreement and NHS England will record the fact that the individuals have been contacted to ensure compliance with the maximum number of contacts outlined as part of consent. Furthermore, in order to ensure that NHS England are able to update the register with which participants are registered with an active trial, and therefore prevent them from being invited to any further trials, NHS England will be provided with regular updates of those registered participants who have consented. This sharing of information is built into the Permission to Contact signing up information and will also be added to the trial consent and participant information.

It should be noted that the following inclusion and exclusion criteria will be used by the recruitment sites during the Screening phase:

INCLUSION CRITERIA

Volunteers must satisfy all the following criteria to be eligible for the study:

● Healthy adults aged 30-55 years

● Able and willing (in the Investigator’s opinion) to comply with all study requirements.

● Willing to allow the investigators to discuss the volunteer’s medical history with their General Practitioner and access all medical records when relevant to study procedures.

● For females only, willingness to practice continuous effective contraception (see below) during the study and a negative pregnancy test on the day(s) of screening, bronchoscopy and vaccination.

● Agreement to refrain from blood donation during the course of the study. Provide written informed consent.

● Have had a complete COVID-19 vaccination course (as one or two intramuscular injections depending on the authorisation schedule) with the last injection at least 30 days before enrolment.

● Sero-suitable (i.e. with evidence of SARS-CoV-2 vaccine-induced antibody responses but no evidence of previous SARS-CoV-2 infection by an authorised serology test. )

● Those with indeterminate levels and no history of laboratory-confirmed SARS-CoV-2 infection may be included or excluded at the Principle Investigator (PI)’s discretion on a case-by-case basis.

EXCLUSION CRITERIA:

Volunteers may not enter the study if any of the following apply (note that the following exclusion criteria is included based on documented safety grounds and has been ethically approved):

● History of laboratory-confirmed SARS-CoV-2 infection.

● Acute upper respiratory infection (URI or sinusitis) in the past 6 weeks

● Prior receipt of any vaccine within ≤30 days prior to enrolment or planned receipt of any vaccine within 30 days after the study vaccination

● Administration of immunoglobulins and/or any blood products within the three months preceding the planned administration of the vaccine candidate.

● Inhaled bronchodilator or steroid use within the last 12 months

● Intranasal steroid use within the last 6 months

● Any confirmed or suspected immunosuppressive or immunodeficient state, including HIV infection; asplenia; recurrent severe infections and use of immunosuppressant medication within the past 6 months, except topical steroids.

● Any autoimmune conditions, except mild psoriasis, well-controlled autoimmune thyroid disease, vitiligo or stable coeliac disease not requiring immunosuppressive or immunomodulatory therapy.

● History of allergic disease or reactions likely to be exacerbated by any component of the AZD1222 vaccine.

● Any history of angioedema.

● Any history of anaphylaxis.

● Pregnancy, lactation or willingness/intention to become pregnant during the study.

● History of cancer (except basal cell carcinoma of the skin and cervical carcinoma in situ).

● * History of serious psychiatric condition likely to affect participation in the study (e.g. ongoing severe depression, history of admission to an in-patient psychiatric facility, recent suicidal ideation, history of suicide attempt, bipolar disorder, personality disorder, alcohol and drug dependency, severe eating disorder, psychosis, use of mood stabilisers or antipsychotic medication).

● Bleeding disorder (e.g. factor deficiency, coagulopathy or platelet disorder), or prior history of significant bleeding or bruising following IM injections or venepuncture.

● History of frequent nose bleeds

● Any other serious chronic illness requiring hospital specialist supervision. Chronic respiratory diseases, including mild asthma (resolved childhood asthma is allowed) Smoking (includes any inhaled product, such as cigarettes and vaping) in the past 6 months OR >5 pack-year lifetime history.

● Chronic cardiovascular disease (including hypertension), gastrointestinal disease, liver disease (except Gilberts Syndrome), renal disease, endocrine disorder (including diabetes) and neurological illness (excluding migraine)

● Seriously overweight (BMI≥40 Kg/m2 ) or underweight (BMI≤18 Kg/m2 )

● Suspected or known current alcohol abuse as defined by an alcohol intake of greater than 42 units every week.

● Suspected or known injecting drug abuse in the 5 years preceding enrolment.

● Use of any medication or other product (prescription or over-the-counter) for symptoms of rhinitis or nasal congestion within the last 3 months Any clinically significant abnormal finding on screening biochemistry or haematology blood tests.

● Grade 1 abnormalities are permissible at investigator discretion.

● Clinically relevant abnormality on chest X-ray

● Any other significant disease, disorder or finding which may significantly increase the risk to the volunteer because of participation in the study, affect the ability of the volunteer to participate in the study or impair interpretation of the study data.

● A history of cerebral venous sinus thrombosis, heparin-induced thrombocytopenia antiphospholipid syndrome or vaccine-induced thrombosis with thrombocytopenia

*As a first-in-human study of this COVID-19 aerosol vaccination delivery method involving bronchoscopies, which are invasive procedures, the study team are not enrolling individuals with a history of any significant health problem (including severe mental health illness) due to the intensity of the study procedures and visits. If this method of vaccine administration is shown to be well tolerated, there should be follow-up studies with less intensive sampling that intend to be open to a much wider spectrum of volunteers.

Individual trial recruitment sites will supply NHS Digital with details of those who have signed up to take part in their trial so that NHS England can suitably capture this information within the NHS England's COVID-19 Vaccine Research Registry. All data that flows to NHS England Digital in this context falls under the controllership of the Data Controller, regardless of whether they themselves are specifically involved in the processing of that data as it flows to NHS England. For this agreement there may be flows from each individual recruitment site. Once the data is received at NHS England then NHS England become controller for that data in their existing role as Data Controller of the NHS England's COVID-19 Vaccine Research Registry.

Due to the nature of trial recruitment sites, they often only become confirmed as sites very close to recruitment, and so NHS England will leave the responsibility with the lead site / data controller to appointment data processors themselves under their own due diligence. This practice aligns with their obligations under GDPR as a data controller and the emphasis will be on the lead site / data controller to appoint appropriate data processors on their behalf. Ordinarily NHS England would carry out these checks, but attempting to do so for this service would cause unnecessary delay to the initial application, as well as potentially multiple and costly amendments thereafter. Therefore, all recruitment sites / data processors and their processing activities will be covered under a suitable processing agreement between themselves and the lead site / data controller which does not require NHS England’s inclusion. Specific details of recruitment sites, such as key contact, location, will therefore not be made known to NHS England unless there is a specific reason to do so.

Imperial College London are partnering with Imperial College Healthcare NHS Trust to support recruitment for COVAXAER01 and act as a Data Processor. Imperial College Healthcare NHS Trust will manage the screening visits that result from the communication to volunteers and further assist recruitment by supplying NHS England with details of those who have signed up to take part in the trial.

No other processing of the data will take place and the data will not be linked with information from any other sources.

Imperial College London and Imperial College Healthcare NHS Trust will not have access to any of the data being disseminated by NHS England under this agreement.

The information from NHS England will be used to facilitate contact with individuals who are potentially eligible and who have indicated willingness to potentially participate in studies/trials of COVID-19 vaccines.

This is expected to result in individuals entering the trials screening process with a view to them participating in the trial with fully informed consent.

The main results from this trial are expected to inform development of a safe and effective multiple vaccine combination against COVID 19.

The primary benefit of using the data will be to allow researchers to identify a suitable cohort and recruit them quickly into the vaccine trial – thus reducing the overall time to recruit into the trials. This is expected to accelerate the delivery of an effective vaccine to treat individuals to manage the COVID-19 outbreak and to save lives.

It is expected that this will reduce the burden on research staff in identifying and contacting potential clinical trial participants. It is anticipated this will also support the Vaccines Taskforce objectives to drive forward, expedite and coordinate efforts to research and then produce a coronavirus vaccine and make sure one is made available to the public as quickly as possible.

COVID vaccine trials are ongoing, some progress quickly whereas others (phase 1 trials) are slower as depend on both the phase of pandemic and the speed of regulatory agency approvals. All studies will generate benefit – either directly impacting the national programme, or via development of future vaccines.