Newsletter 117

HRA MakingTransparencyEasy

By Till Bruckner, Caroline Struthers and Mandy Payne

After decades of talking about the problem of transparency in research, the UK is finally striding forward with important new initiatives that we hope will be copied globally.

Clinical trial transparency is not about adding bureaucracy and hampering innovation, it is about protecting patients and the quality of research. Registering clinical trials publicly, even before they start, helps other scientists discover who is currently researching which treatments, preventing needless duplication of medical research efforts. Wasted research comes at mind-boggling financial and also human costs, as patients in clinical trials may be subjected to unnecessary risk. And by requiring investigators to declare publicly at the outset what their study will be measuring, it is harder to manipulate the resulting data at a later stage, either to distort the evidence or for financial gain or glory.

With this in mind HealthWatch welcomed the announcement on 20 October this year from the NHS's Health Research Authority (HRA), one of the bodies that regulates UK research, of a new system to ensure that every single clinical trial will be listed on a trial registry from the outset (for more on this, see below).

A further welcome announcement came soon after, on 11 November 2021 from the National Institutes for Health Research (NIHR), another UK body that works with the NHS, government and universities to fund, enable and deliver health and social care research. A new Open Access policy will require all peer-reviewed research articles arising from NIHR-funded research studies immediately to be made open access under an open licence – this means that the published results of research funded by UK taxpayers and others will be available to read online for free. This change will apply to all peer-reviewed articles submitted for publication on or after 1 June 2022.

Against the backdrop of these new UK transparency initiatives, the HRA held its first “Make it public” conference on 3-4 November 2021. This event showcased the impact of transparency on health and social care studies in the UK and featured talks from the regulators, the funders, patient representatives and those responsible for clinical trial registries.

The regulators - HRA

The Health Research Authority (HRA) is one of the bodies responsible for regulation and governance of research in the UK. Naho Yamazaki, Head of Policy and Engagement at the HRA, confirmed that their traditional reluctance to adopt sanctions for not reporting clinical trial results has not changed. While the HRA had made a “commitment” to impose sanctions, it would “proceed carefully” and only after engaging with stakeholders. There is no timeline for when HRA will impose sanctions. HealthWatch has in the past repeatedly called for the adoption of sanctions with teeth – if the HRA is left to its own devices, this seems unlikely to happen in the foreseeable future.

On the positive side, the HRA has made impressive progress with all other elements of the UK’s national #MakeItPublic strategy. In a world first, the HRA itself will in future automatically register all clinical trials after they receive ethics approval, thereby ending the problem of unregistered trials. It is already a requirement that all clinical trials are registered with a World Health Organisation (WHO) recognised registry before the first participant is recruited to a study, nevertheless many are not. From January 2022, in partnership with the London-based globally recognised clinical trial registry ISRCTN, the HRA will automatically register all UK drug trials as part of the study approval process. The process will later be rolled out to cover all interventional trials. The HRA has already developed clear guidance for researchers and set up a system to monitor whether trial results are made public, which should be within one year of study end.

HealthWatch and our partners at TranspariMED have long called for this initiative, and we are delighted that it is at last being set up. By the end of 2022 trial results should also be appearing on the HRA’s website. For the key milestones see TranspariMED’s report.

The HRA also encourages reporting of results in plain English (lay summaries), but this is not mandatory.

The trial registry - ISRCTN

Claire Veryard from the London-based trial registry ISRCTN (which stands for "International Standard Randomised Controlled Trial Number") announced the registry's formal partnership with the HRA, which will in effect make ISRCTN the UK’s national trial registry going forward. ISRCTN launched a new “output table” this year, allowing those running trials to share a wealth of information on the registry, including statistical analysis plans, preprints, funder reports, and links to external platforms. ISRCTN will continue to develop its existing system of using email prompts to remind researchers to update registry data and upload trial results regularly.

The regulators - MHRA

Martin O’Kane from the Medical and Healthcare products Regulatory Agency (MHRA) provided an overview of the agency’s current and future efforts to improve clinical trial transparency. The new, post-Brexit, medicines regulator continues to send reminders to researchers to make the results of older drug trials public on the European trial registry as required by MHRA. Current compliance by UK sponsors is a high 85%, but the MHRA continues to aim for 100%. The Good Clinical Practice (GCP) Inspectorate within MHRA is notified when sponsors fail to upload results.

O’Kane noted that current UK law contains no requirements to register trials or make their results public, but that the recent Medicines and Medical Devices Act has provided a “once in a lifetime opportunity” to mandate these steps. Before the end of 2021, the MHRA would launch a consultation on options for making reporting of trial results within 12 months of trial completion compulsory. The MHRA is also considering introducing sanctions for non-reporting, and making the involvement of patients and the public in the design of clinical trials a legal requirement.

Going forward, the MHRA will work to align trial registration forms with those required by the HRA and the ISRCTN, hopefully making the process easier and less time-consuming for researchers. O’Kane noted that the close collaboration of the MHRA with the HRA, NIHR and NHS really added value during the UK’s widely praised Covid-19 clinical research efforts.

Patients in research

On keeping participants informed was explored by Jo Taylor, a secondary breast cancer patient. She said that health professionals were not telling patients that primary breast cancer - even when successfully treated - can often result in metastatic breast cancer. They might not even be told the red flags to look out for because, apparently, “it’s too scary for people”.

As a result, people who may benefit from new treatments for metastatic breast cancer miss out on opportunities to take part in research on treatments.

Metastatic breast cancer is not a chronic condition – it’s incurable and terminal. But there are disease-mitigating treatments, and Taylor claimed that patients affected are not being informed about the opportunities to take part in research, so are excluded from trials until often it’s too late, whereas being in a trial of an effective new treatment could have given them more time.

Communicating with research participants

An excellent new communications toolkit developed by Parkinson’s UK deserves to be adopted by all research funders in all areas of health research – possibly even as a condition of receiving funding. In this panel session Lynn Laidlaw, the only patient participant, made a deep impression. Having started as a research participant herself, she is now co-producing research where she will be holding celebration events with the participants along with informing them of the results of the study.

When she was asked why researchers should go to these lengths, Laidlaw replied that it was extremely rude not to! To assume people will ask for the results if they want to know them, and that if they don’t ask, they don’t want to know, was an attitude instantly recognised by our reporter Caroline Struthers from her experience as a “healthy control” in observational studies.

It comes down to the current research culture. Researchers are incentivised to publish in the Lancet, but not to share their results with participants. Yet, without them the research could not happen. Laidlaw advocated using the small amount of power you have as a research participant to refuse to take part unless the results are going to be shared. She now does this every time.

In the conference’s closing remarks, HRA’s CEO, Professor Matt Westmore, observed: “Seventy-five per cent of UK trials publish their results. This is not perfect, but against a global figure of 50 per cent this is momentous and world leading.”

HealthWatch and TranspariMED are keeping an eye on the new developments as they are implemented in 2022.

For more about the HRA transparency initiatives, read their full strategy report.

Reported by Till Bruckner, TranspariMED; Caroline Struthers, UK EQUATOR Centre; Mandy Payne, HealthWatch Newsletter editor.