University of Oxford

Academic Institute

No

DARS-NIC-411161-G4K7X-v3.2

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.

The trial has co-primary endpoints: 1) Time taken to self-reported recovery; and 2) hospitalisation and/or death. 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. 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. 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.

05/11/2021

CV19: Regulation 3 (4) of the Health Service (Control of Patient Information) Regulations 2002

Statutory exemption to flow confidential data without consent

Recurring

TRE