Comparing COVID-19 Vaccine Schedule Combinations (Com-COV)

This Data Sharing Agreement authorises the use of information voluntarily provided to NHS Digital 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, University of Oxford, by NHS Digital as a data processor for the purpose of supporting recruitment to participate in a COVID-19 vaccine trial being run by University of Oxford.

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

NHS Digital 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 (PtC) 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 Digital 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 Digital 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 Digital 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 Digital, as data processor acting on behalf of University of Oxford, will be sending the email to eligible participants.

This request relates specifically to a vaccine trial. This is a Single-blind, randomised prime-boost vaccine administration study comparing COVID19 vaccine schedule combinations.

On the 2nd December 2020 the MHRA granted emergency authorisation for a vaccine against COVID-19, ‘COVID-19 mRNA Vaccine BNT162b2’. This was the first in what are expected to be multiple vaccines approved for use against COVID-19. . Most of these are expected to be approved as a two-dose regimen, using the same vaccine for both the initial (prime) and subsequent (boost) dose. There are likely to be significant logistical challenges immunising large portions of the population. There would be significant advantages to having flexible immunisation programmes whereby the second vaccine dose is not necessarily the same as the first dose. Accordingly, this study will determine the safety as well as the immune responses to a variety of combinations of prime/boost schedules for candidate COVID-19 vaccines that are potentially to be deployed in the UK. The vaccines to be studied in this protocol will primarily be determined by those made available to the Department of Health and Social Care (DHSC) for population use, but for the purposes of this articular application, the aim is to recruit participants to test combinations of ChAdOx1 nCOV-19 (developed by University of Oxford / AstraZeneca) and BNT162b2 (developed by Pfeizer).

The primary objective is to determine whether the immune response in COVID seronegative participants to immunisation with heterologous prime/boost COVID-19 vaccines regimens (boosted at D28) is non-inferior to that observed following immunisation with approved homologous prime-boost regimens (boosted at D28).

The secondary objectives are to determine whether the immune response in COVID seronegative participants to immunisation with heterologous prime/boost COVID-19 vaccines regimens across all dosing intervals is non-inferior to that observed following immunisation with approved homologous prime-boost regimens, and the reactogenicity and safety of heterologous & homologous prime/boost schedules of COVID-19 vaccines.

The aim for this application is to recruit a total of total of 820 participants, consisting of an Immunology cohort receiving their booster vaccine dose after 28 days (n=100) and a General cohort (n=720). Half of the general cohort participants (N-360) will receive their booster vaccine after 28 days, and half will receive their booster vaccine after 84 days.

Within the immunology cohort participants will be randomised 1:1:1:1 to the following arms receiving their booster vaccine dose after 28 days:

• Prime ChAdOx1 nCOV-19, Boost ChAdOx1 nCOV-19

• Prime ChAdOx1 nCOV-19, Boost BNT162b2

• Prime BNT162b2, Boost BNT162b2

• Prime BNT162b2, Boost ChAdOx1 nCOV-

Within the general cohort participants will be randomised 1:1:1:1:1:1:1:1 to the following arms:

• Prime ChAdOx1 nCOV-19, Boost ChAdOx1 nCOV-19 28 day boost

• Prime ChAdOx1 nCOV-19, Boost BNT162b2 28 day boost

• Prime BNT162b2, Boost BNT162b2 28 day boost

• Prime BNT162b2, Boost ChAdOx1 nCOV-19 28 day boost

• Prime ChAdOx1 nCOV-19, Boost ChAdOx1 nCOV-19 84 day boost

• Prime ChAdOx1 nCOV-19, Boost BNT162b2 84 day boost

• Prime BNT162b2, Boost BNT162b2 84 day boost

• Prime BNT162b2, Boost ChAdOx1 nCOV-19 84 day boost

There will therefore be a sum total of 205 participants receiving each different permutation of vaccine, 25 of whom will be in the Immunology cohort with booster vaccine dose after 28 days, 90 in the General Cohort with booster vaccine dose after 28 days and 90 in the General Cohort with booster vaccine dose after 84 days.

The initial mailout will aim for around four / five times the number of potential participants to be recruited and therefore the estimate is for around 4,100 individuals to be contacted.

Although this application relates to the combining of two commercial vaccines, there is no commercial element specifically attached to this application itself, the purpose of which is about influencing national vaccine rollout strategy. Although results may influences the manner in which the commercial firms role out vaccines in future, this application relates solely to an academic exercise.

Although AstraZeneca and Pfeizer have allowed the use of their vaccines for this trial, they have no responsibilities as to how the trial is conducted and therefore University of Oxford remain the sole Data Controller for this application.

NHS Digital will extract a list of patients meeting the following criteria, where that criteria can be ascertained using the PtC registry:

INCLUSION CRITERIA:

1. Participant is willing and able to give written informed consent for participation in the trial.

2. Male or Female, aged 50 years or above and in good health as determined by a trial clinician Participants may have well

controlled or mild-moderate comorbidity.

3. Female participants of childbearing potential must be willing to ensure that they or their partner use effective contraception from 1 month prior to first immunisation continuously until 3 months after boost immunisation.

4. In the Investigator’s opinion, is able and willing to comply with all trial requirements.

5. Willing to allow their General Practitioner and consultant, if appropriate, to be notified of participation in the trial.

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

7. Agreement to refrain from blood donation during the course of the study

EXCLUSION CRITERIA:

The participant may not enter the trial if ANY of the following apply:

1. Receipt of any vaccine (licensed or investigational) other than the study intervention within 30 days before and after each study vaccination (one week for licensed seasonal influenza vaccine or pneumococcal vaccine).

2. Prior or planned receipt of an investigational or licensed vaccine or product likely to impact on interpretation of the trial data (e.g. Adenovirus vectored vaccines, any coronavirus vaccines).

3. Administration of immunoglobulins and/or any blood products within the three months preceding the planned administration of the vaccines.

4. Any confirmed or suspected immunosuppressive or immunodeficient state; asplenia; recurrent severe infections and use of immunosuppressant medication within the past 6 months, except topical steroids or short-term oral steroids (course lasting ≤14 days).

5. History of allergic disease or reactions likely to be exacerbated by any component of the study vaccines.

6. Any history of angioedema.

7. Any history of anaphylaxis or if they have been advised to carry an adrenaline auto-injector.

8. Pregnancy, lactation or willingness/intention to become pregnant within 3 months post boost vaccine.

9. Current diagnosis of or treatment for cancer (except basal cell carcinoma of the skin and cervical carcinoma in situ).

10. History of serious psychiatric condition likely to affect participation in the study.

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

12. Continuous use of anticoagulants, such as coumarins and related anticoagulants (i.e. warfarin) or novel oral anticoagulants (i.e. apixaban, rivaroxaban, dabigatran and edoxaban).

13. Suspected or known current alcohol or drug dependency.

14. 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.

15. Severe and/or uncontrolled cardiovascular disease, respiratory disease, gastrointestinal disease, liver disease, renal disease, endocrine disorder and neurological illness (mild/moderate well .controlled comorbidities are allowed).

16. History of active or previous auto-immune neurological disorders (e.g. multiple sclerosis, GuillainBarre syndrome, transverse myelitis). Bell’s palsy will not be an exclusion criterion

17. History of laboratory confirmed COVID-19 prior to enrolment (history of SARS-CoV-2 detection by PCR or antibody to

SARS-CoV-2).

18. Significant renal or hepatic impairment.

19. Scheduled elective surgery during the trial.

20. Participant with life expectancy of less than 6 months.

21. Participants who have participated in another research trial involving an investigational product in the past 12 weeks.

22. Insufficient level of English language to undertake all study requirements in opinion of the Investigators.

The inclusion and exclusion criteria noted above is based on the information provided by cohort members on the permission to contact dataset (where it can be obtained from this dataset), and is not collected from other NHS data sources. Some of the above inclusion and exclusion criteria will be used by the sites during the Screening phase.

NHS Digital will identify all individuals within the PtC dataset meeting the relevant criteria and will extract their names, 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, such as an uneven ratio of males to females, subsequent mail outs may restrict the required criteria to a greater degree than previously, for example, only requesting details for male participants as opposed to both males and females. 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 Digital will write to the individuals in the subset inviting them to participate within the trial using ethically approved text provided by University of Oxford. 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 Digital 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 Digital 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 Digital 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 (see supporting document SD3 for further details).

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 Digital can suitably capture this information within the Permission To Contact registry. All data that flows to NHS 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 Digital. For this agreement there may be flows from each individual site. Once the data is received at NHS Digital then NHS Digital become controller for that data in their existing role as controller of the Permission To Contact Registry.

Due to the nature of trial recruitment sites, they often only become confirmed as sites very close to recruitment, and so NHS Digital 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 Digital 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 Digital’s inclusion. Specific details of recruitment sites, such as key contact, location, will therefore not be made known to NHS Digital unless there is a specific reason to do so.

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

University of Oxford will not have access to any of the data being disseminated by NHS Digital under this agreement.

The information from NHS Digital 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 recruit participants for the clinical study/trial in a manner which:

• Enables individuals to volunteer in advance to participate in COVID-19 vaccine trials as an alternative to other potentially more intrusive mechanisms, e.g. sharing data with researchers about individuals under section 251 consents or COPI notices, which although lawful is initially less transparent.

• Allows researchers to identify a suitable cohort and recruit them quickly into the vaccine trials – thus reducing the overall time to recruit into the trials and to accelerate the delivery of an effective vaccine to treat individuals to manage the COVID-19 outbreak and to save lives.

• Reduces burden on research staff in identifying and contacting potential clinical trial participants.

• Supports 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.

Yielded Benefits is not a requirement for new applications.