ATEMPT: Antihypertensive Treatment in Elderly Multimorbid Patients (Pilot Study)

It is unclear how to best manage blood pressure (BP) in older patients or in the presence of many underlying health problems, in particular when BP is not very high. The Antihypertensive Treatment in Elderly Multimorbid Patients (ATEMPT) Clinical Trial (Pilot) aims to improve the understanding of BP management in older, multimorbid people by comparing the effectiveness and safety of changing the number of prescribed antihypertensive drugs in two similar groups of such individuals. The study additionally aims to assess the acceptability and tolerability of the intervention (using patient-reported outcomes) and to rule out any major excess harms (risk of serious adverse events). If the Pilot shows that an intervention can lead to important changes in BP, this information will help to assess whether a larger trial is feasible and beneficial to investigate the effect of the intervention on clinical outcomes. An additional aim is to test the feasibility of the main components of the trial, namely participant recruitment, randomisation, delivery of treatment, and remote assessment of trial outcomes and to obtain information about resource requirements for the main trial.

ATEMPT is a two-armed, parallel-group, partially blinded randomised controlled trial, comparing more versus fewer anti-hypertensive medications in older patients (≥65 years) with multimorbidity or polypharmacy who are willing to have their BP-lowering treatment changed. Participants eligible for the trial will be randomised to one of the two treatment arms A or B:

Arm A (more antihypertensive drugs): up to two more classes of antihypertensive drugs, vs

Arm B (fewer antihypertensive drugs): up to two fewer classes of antihypertensive drugs.

As a pragmatic trial, ATEMPT will include participants with different background antihypertensive treatments and a wide range of baseline BP. ATEMPT is not a trial of specific types of medications or a particular BP target, but rather a trial of “more” versus “fewer” antihypertensive treatments.

For the ATEMPT Clinical Trial (Pilot), the University of Oxford will submit two separate data applications to NHS Digital. This request is for the demographic data of individuals who meet specified criteria, with the aim being to identify a pool of potential participants for the Pilot study. The data requested are name, address, gender, and date of birth.

The search criteria will define the age, geographical location, and certain health criteria required for participation in the trial. The data obtained with confidentiality advisory group (CAG) support will initially be used to support recruitment activities as follows. The name and address will be used to send individuals an invitation letter to take part in the trial, age and gender will be used by the Chief Investigator to balance enrolment.

The data requested from NHS Digital for this application is record level, identifying data, and for individuals from the Thames Valley area. The Thames Valley represents an area large enough to obtain the target number of participants but is practical for research team members visits to participants when blood tests are required. The data is requested without consent as it would not otherwise be possible to identify a suitable pool of participants for this remote trial considering that an estimated 20,000 potential participants would need to be identified to recruit 200 participants for this pilot study. Once 200 participants have been recruited into the pilot study, the second data application to NHS Digital will request the health outcomes of these participants following a period of BP management intervention.

The data requested in this application have been minimised. The study team will provide NHS Digital with a search query to select individuals aged 65 years or more with three or more chronic conditions diagnosed within a 5-year time window prior to the latest assessment date. The selection of chronic conditions of interest will be based on 3-character ICD codes and individuals with a recorded diagnosis of heart failure will be excluded. The search query will be provided twice, each time restricted to individuals who live within different regions in the Thames Valley area and are alive at the time of data sharing with the research team. This will enable the list of potential participants to be provided in manageable batches and permit the contact of all individuals on a given list within a month. After checking, the data participants will be invited by post for consideration of participation into the trial. At the end of enrolment all data for those individuals not taking part in the trial will be deleted.

The University of Oxford is the sole data controller who will also process data for this study. During recruitment and under the direction of the University of Oxford, CFH Docmail Ltd will process personal data (names and addresses) in order to print and post the invitation letters to potential participants.

The data will be stored and processed at the University of Oxford. Other than the processing carried out by CFH Docmail Ltd the data supplied by NHS Digital will not be released to any other organisation or used for any other purpose.

There are three other organisations involved in the study which are not processing NHS Digital data. Midland Pathology will be analysing participant blood samples, Twilio will be facilitating SMS notifications (no personal data in the messages) and Pharmacy 2U will be providing contact details of potential participants from their customer base to aid recruitment, dispensing and delivering prescriptions and providing repeat prescription information as safety data.

The trial is funded by research grants from the National Institute of Health Research (NIHR) Oxford Health Biomedical Research Centre and the Oxford Martin School.

The University relies on GDPR Article 6(1)(e) of the General Data Protection Regulation (GDPR) to process personal data where processing is necessary for a task carried out in the public interest or in the exercise of official authority vested in the University. In this instance the public interest task is research. The University also relies on Article 9(2)(j) of the GDPR to process special category data (in this case health data) where processing is necessary for scientific research purposes.

The processing of data outlined in this application occurs without the consent of the data subjects initially. Any risk to individual data subjects from loss of data is minimized by a number of robust security processes. Inconvenience to data subjects is minimized by sending invitation letters by post in which it is clear that they do not need to take part in the study. These issues have been considered by both the Confidentiality Advisory Group and the Research Ethics Committee. There are no alternative, less intrusive ways of achieving the purpose.

NHS digital will extract the details of patients that are aged 65 and older, residing in the Thames Valley (specific postcodes provided) with at least 3 co-morbidities diagnosed in the 5 years prior to the search, excluding those with a previous diagnosis of heart failure (ICD code I50). Patients who are deceased would be excluded. This information will be requested in up to 2 batches based on subsets of postcodes. If enrolment targets are met before the second batch of demographics data have been disseminated, the University of Oxford will inform NHS Digital as soon as possible, halting the production and dissemination of personal details which are no longer required.

NHS Digital will provide to the University of Oxford a file containing the following identifying data for potentially eligible participants within the specified postcodes for a given request: Name, address, gender, and date of birth. The University will then undertake further work to ascertain eligibility. The data will be stored in the ATEMPT pre-screening database.

The University will write to the potential participants inviting them to take part in the trial. In order to efficiently print and mail invitation letters, batches of personal data (name and address) will be sent securely to CFH Docmail Ltd who will process these data in order to print and post the invitation letters. The letters will be sent out gradually in smaller batches across one month, enabling the study team to stop sending letters as soon as there are enough participants enrolled on the study. Data is retained by CFH Docmail for one month after an invitation letter is mailed to a participant at which point the data is deleted. The University of Oxford may send one reminder to those who have not responded within that timescale.

The potential participants will be able to use a website address provided in the letter to find out more about the trial and a unique access code to log in and register their interest. The name and address of those consenting to take part will be copied to the ATEMPT study database at the point of e-consent and then participant name, address and other identifiable information will be collected directly from the participant.

At the end of enrolment the University of Oxford will delete data of all individuals not taking part in the trial. Participants who have provided their consent for taking part in the trial will have their identifiable information sent to NHS Digital under a new data sharing agreement to obtain Hospital Episode Statistics data for participants (safety data). Given identifiable information will be provided under consent for the subsequent agreement, all NHS Digital data provided using s251 approval for this original agreement will be deleted at the end of enrolment.

The ATEMPT pre-screening database and ATEMPT study database are not linked to any other databases. Data is stored securely by the University of Oxford in a high compliance system (HCS) suitable for storing personal and special category data, and data can only be accessed by study team members with a level of access based on their role. The HCS is accessed remotely on a university device and requires a unique username and password and two factor authentication. Data is not being matched to publicly available data. The data received from NHS Digital will only be accessed by individuals in the ATEMPT Study Team who have authorisation to access the data for the purposes described, all of whom are substantive employees of the University of Oxford and have been appropriately trained in data protection and confidentiality.

Where names and addresses are transferred to CFH Docmail to print and mail invitation letters, only CFH Docmail staff with appropriate authorisation and who need to access the data in order to fulfil their job role are allowed access to the data. These staff are all appropriately trained in data protection and confidentiality. They are required to sign a confidentiality agreement on an annual basis and are subject to refresher training and updates relating to data protection, GDPR and confidentiality on a regular basis, at least once a year. Data access at CFH Docmail is arranged by Security Group membership and Access Control Lists. Only restricted authorised production personnel can access compiled files. CFH Docmail have two employed data protection officers who would be responsible for the investigation and response to any data breach.

During the pandemic, where feasible, CFH staff are currently working from home and accessing their infrastructure via a secure VPN. The VPN is configured to provide users with the same access that they would have if they were on the cabled CFH Docmail internal network and is secured on an individual basis, with two factor authentication being required.

The research agenda, plan of investigation and monitoring of the execution of the ATEMPT trial is overseen by a trial steering committee. Members of a patient group, or individuals able to contribute to the wider public perspective are involved in the committee and review public-facing outputs.

The main trial results from the ATEMPT Pilot Study are expected in 2022 with a publication towards the end of that year.

The results will be disseminated widely, including presentation at relevant conferences such as the European Society of Cardiology annual meeting and publication in an open-access, high-impact medical journal such as the European Journal of Cardiology. Further academic papers (including a protocol paper and results of remote recruitment and management of the trial) will be published in open-access, high impact, peer-reviewed journals and on the trial website.

A non-technical summary of the main study findings will be provided to participants and other interested groups and published on the study website.

The data will be de-identified at the end of the study and only anonymised results will be used in publications.

The findings from this pilot study will be used to inform and plan an adequately powered major, multinational Randomised Controlled Trial. Additionally, the experience gained from utilising IT-enabled systems to remotely recruit and monitor participants will be evaluated with a view to expanding the use of the software to manage other research trials within the department and wider University. The online system for the ATEMPT trial has been developed in conjunction with members of the public aged 65 years or older in order to ensure that it is as simple and easy to use as possible.

This data application will enable an eligible group of potential participants to be identified and recruited into the ATEMPT clinical trial (pilot).

It is hoped that the results from the ATEMPT trial will be relevant for the management of hypertension in older people with multimorbidity or polypharmacy, a patient group for whom currently the treatment effects of pharmacological blood pressure (BP) reduction remains uncertain. These patients have been underrepresented or excluded in previous research, thus, leaving an important gap in our understanding of treatment effects. One key reason for the existing gap in evidence is the challenge of recruiting sufficiently large numbers of older and multimorbid patients into clinical trials. This pilot study aims to address this challenge by recruiting approximately 200 participants aged 65 or over who have at least 3 long-term health conditions or are taking at least 5 medications in addition to any being taken to manage blood pressure.

The findings from this pilot study are intended to provide the feasibility required to inform the planning of a larger, multi-national, home-based study to assess the effect of treatment changes on patient-important outcomes. This trial could impact the treatment regime of millions of patients in the UK.

The study is designed to minimise the burden of participation to patients. There is no need for clinic attendance. Participation and follow-up will take place at home using a bespoke IT system with much of the data collected remotely.

The experience of using bespoke IT-enabled systems to remotely recruit and monitor participants will, if shown to be effective, be considered for use in the recruitment and study management of other research trials. This could provide the means for other researchers to not only streamline research processes but also include participants in trials who historically are reluctant or unable to participate in research trials due to the demands made of them to attend research visits. For instance, research suggests that the vast amount of research findings are based on studies that have included participants in close proximity to specialised centres, men, and those who have fewer comorbidities. This leaves a gap in research for the majority of the population in the UK to whom research findings are being applied. This study should not only encourage participation of such patients but will assess the extent to which conduct of trials can be made more efficient and hence affordable.

Yielded Benefits is not a requirement for new applications.