A Phase II, randomised, single-blind, platform trial to assess safety, reactogenicity and immunogenicity of COVID-19 vaccines in pregnant women in the United Kingdom (Preg-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, St George’s University of London, by NHS Digital as a data processor for the purpose of supporting recruitment to participate in a COVID-19 vaccine trial being run by St George’s University of London.

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 St George’s University of London, will be sending the email to eligible participants.

This request relates specifically to a vaccine trial. This is A Phase II, randomised, single-blind, platform trial to assess safety, reactogenicity and immunogenicity of COVID-19 vaccines in pregnant women in the United Kingdom

Pregnant women should be provided with a balanced and clear assessment of their risk of COVID-19 in pregnancy, taking into account their individual circumstances, local practices and available evidence. They should also be counselled with a balanced summary of the potential direct and indirect benefits of COVID-19 vaccines, and the current lack of safety data should be acknowledged. COVID-19 vaccination should not be withheld from women who have received adequate counselling and understand the uncertainties, potential harms, and potential benefits of these vaccines. However, there are important unanswered questions regarding the reactogenicity, safety, immunogenicity, and persistence of immunity in the mother and infant, as well as the efficiency of placental transfer of antibodies and the optimal schedule for pregnant women, it is important that such data are gathered in a systematic and controlled manner. In doing so, evidence based guidelines can be developed which will then benefit all pregnant women. There is a widespread call to gather such evidence for use of COVID-19 vaccines in pregnant women; however, it is possible that the window of opportunity for doing this is closing as more women receive vaccines routinely. A number of advantages therefore exist in recruiting pregnant women into a pragmatic clinical trial in which they all receive a COVID-19 vaccine (rather than a placebo). Using a platform design Preg-CoV will allow inclusion of new COVID-19 vaccines as they become licensed, as well as rapidly address new questions of relevance to the vaccine programme as they arise (different intervals, one dose schedules etc).

The aim is to recruit 900 participants for the trial. 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 4,500 individuals to be contacted.

The applicant has met with representatives of organisations such as The Miscarriage Association and SANDS to ensure that the content for the approved communication to members of the NHS Digital COVID-19 Vaccine Research Registry has been suitable worded to take account of the potential sensitivities around recruiting participants for a trial of this nature.

Although this application relates to the use of 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 influence the manner in which the commercial firms role out vaccines in future, this application relates solely to an academic exercise.

Although AstraZeneca, Pfeizer and Moderna have allowed the use of their vaccines for this trial, they have no responsibilities as to how the trial is conducted and therefore St. George’s University of London remain the sole Data Controller for this application. This also applies to any other commercial vaccine manufacturers that make their vaccines available for use in this trial in future.

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. Healthy women, or women with stable underlying medical conditions, 18 - 45 years of age, between 13 0/7 and 34 0/7 weeks’ gestation on the day of planned vaccination, with an uncomplicated, singleton pregnancy, and who are at no known increased risk of severe COVID-19 or obstetric complications

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

3. 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

4. Willing and able to give informed consent prior to study enrolment

5. No contraindication to the specific vaccine to be administered in the study, according to the Green Book.

EXCLUSION CRITERIA:

1. Previous microbiological (based on a positive SARSCoV-2 NAAT result) diagnosis of COVID-19

2. Administration of immunoglobulins and/or any blood products within the 3 months preceding the planned administration of the study vaccine candidate (with the exception of anti-D immunoglobulin)

3. Previous vaccination with any COVID-19 vaccine (main cohort); prior receipt of one dose of a COVID-19 vaccine is permitted (sub-study)

4. Any confirmed or suspected immunosuppressive or immunodeficient state; chronic administration (defined as more than 14 continuous days) of immunosuppressant medication within the past 3 months, except topical steroids or short-term oral steroids (course lasting ≤ 14 days).

5. Any contraindication to the specific vaccine to be administered in the study, according to the Green Book or to the Summary of Product Characteristics for a specific vaccine

6. Current major illness of the mother or conditions of the fetus that, in the investigator’s judgment, will substantially increase the risk associated with the participant’s participation in, and completion of, the study or could preclude the evaluation of the participant’s response, including but not limited to the following:

• Uncontrolled gestational hypertension

• Preeclampsia-eclampsia

• Placental abnormality

• Polyhydramnios or oligohydramnios

• Significant bleeding or blood clotting disorder

• Uncontrolled gestational diabetes

• Any signs of premature labor with the current pregnancy or having ongoing intervention (medical/surgical) in the current pregnancy to prevent preterm birth

• Prior stillbirth or neonatal death, preterm delivery (≤34 weeks), or previous infant with a known genetic disorder or major congenital anomaly.

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 St George’s University of 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 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.

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.

St George’s University of London 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.