The UK government is planning to monitor all clinical trials. But will the new system work?
Following an enquiry by parliament that showed that many clinical trials conducted in the UK still do not report results, the government is now developing plans for a monitoring system to ensure that in future, every clinical trial is registered and reported.
(The system is likely to be based on the records of all Research Ethics Committees (RECs) countrywide, as every clinical trial conducted on UK soil has to pass through one of these RECs for approval before it begins. The Health Research Authority in London centrally gathers all REC records, and so already holds all information required to monitor whether trials are subsequently registered and make their results public.)
However, recent actions by key public bodies cast doubt on whether the new system will really put an end to the impunity that caused the scandal of hidden and unreported clinical trials in the first place:
The Health Research Authority (HRA) is refusing to make public legal advice it obtained - following a recommendation by parliament - on the possibility of imposing sanctions on individuals and institutions who conduct unethical medical research. This effectively precludes public debate on sanctions, which are an essential element of any credible accountability system. Worringly, the HRA is also the public body leading the process of designing the new system.
The Medical Research Council (MRC) is refusing to release line-by-line audit data that would make it possible for the public to identify which individuals and institutions are violating medical research ethics and wasting public money. This runs directly contrary to fundamental democratic transparency norms.
Against this backdrop, to inform public and expert debate, TranspariMED has set out eight transparency and accountability benchmarks for the new monitoring system.
Alternatively, details on each benchmark are provided below.
The eight benchmarks for the UK's national monitoring system:
The system should capture all interventional clinical trials (as defined by the WHO) conducted on UK soil, including device trials and trials of non-drug interventions, regardless of sponsor type and location.
The system should ensure that ‘no trial is left behind’. Any trials that are found to be unregistered and/or inadequately reported within the time period covered by one audit should ‘remain on the books’ until all outstanding issues have been resolved, or the trial is formally written off as non-registrable or its results as non-recoverable. The analogy of bank loans may be useful: a bank may either recover or write off a loan, but no loan file is ever dropped without a formal close-out.
The system should be designed to be as efficient as possible in order to minimise the administrative burden it places on trial sponsors and PIs, while also minimising the costs of managing the system itself. A start-up investment into streamlining, integrating and automating audit processes to the maximum extent possible will save all stakeholders involved considerable time and resources in the long term. Note in this context that the NHS successfully manages millions of patient records; managing data on the less than 2,000 trials conducted in the UK every year should not be expensive.
The system should incorporate sanctions, including debarment from conducting future trials and financial penalties. Sanctions should be automatically triggered according to clear, well-defined, objective and transparent criteria, rather than being imposed on a subjective, discretionary, case-by-case basis. Note in this context that the Declaration of Helsinki clearly and unequivocally states that any failure to adequately register and/or report the results of any clinical trial is a breach of medical research ethics. The current impunity for researchers that behave unethically must end.
Recommendation: In order to enable an informed debate and consultative process on the issue of sanctions, the Health Research Authority should immediately make public the legal advice it obtained in this regard, and circulate this advice to Research Transparency Strategy Group members and other key stakeholders.
The system should actively support trial sponsors in complying with global best practices. Support mechanisms worth considering in this context include:
(a) production and dissemination of user-friendly guidance to managing entries on the three commonly used registries (EUCTR, Clinicaltrials.gov and ISRCTN)
(b) setting up a national helpdesk for PIs and trial sponsors
(c) setting up a peer-to-peer support network (see here for an interesting model)
(d) conducting surveys to identify barriers to good registry management encountered by sponsors and PIs (see here for examples), and working with regulators and trial registries to remove these barriers
In order to support progressive improvements in clinical trial transparency, the system should aim to continually improve the level of clinical trial transparency in the UK by setting benchmarks based on global best practices (rather than only auditing narrow regulatory compliance). The system should combine this with a feedback loop through which all trial sponsors and PIs receive automated email updates on their performance against global best practices.
For example, the system should capture data on registration timepoint (pre or post), adherencto easy-to-assess CONSORT elements (e.g. presence of registry ID number in journal abstract), and accuracy of status (ongoing/completed) stated on registries. Capturing each of these data points manually would take less than one minute per trial.
Note that assessing trials’ performance beyond narrow regulatory compliance would be fully in line with the Health Research Authority’s mandate. Without imposing any new regulations, red tape or sanctions, a broad audit scope coupled with direct feedback to stakeholders would significantly drive voluntary adherence to global best practices.
Recommendation: During the next meeting, the Research Transparency Strategy Group should solicit members’ suggestions for elements of trial registration and reporting to include in the audit scope, and the Health Research Authority should present a proposed list of audit elements in the draft strategy for public consultation.
All data points collected during the audit process should be made publicly available. The system should regularly make public audit reports containing line-by-line data on every individual trial and its performance against every audit criterion. In the case of trials that have been registered, each trial should be identified with its registry ID number(s). In the case of trials that have not been registered, sufficient information should be provided to allow external stakeholders to clearly identify the trial in question and those responsible for ensuring its registration, i.e. at a minimum the names of the trial’s funder, sponsor, and PI.
Recommendation: The Medical Research Council should immediately publish the complete line-by-line data set from its most recent trial audit, allowing individual trials to be identified, and commit to routinely making all data gathered during future audits public. This would set a strong precedent for transparency, and send a clear signal that that in future, public bodies will no longer shield non-compliant medical research stakeholders from public scrutiny.
All data points collected during the audit process should be made publicly available in an accessible format to allow secondary analysis by external parties. Audit reports should include freely downloadable data sets to facilitate their use by meta-researchers.
Note that in the past, comprehensive clinical trial audits (i.e. audits that also capture all unregistered trials in a cohort) were always limited to individual institutions or Research Ethics Committees. Nation-wide audit data will constitute an unprecedented, unique and invaluable resource for meta-researchers.
TranspariMED will continue to follow and support the work of the Research Transparency Strategy Group set up by the Health Research Authority over the coming weeks and months.
Universities that want to improve their clinical trial transparency can use TranspariMED's collection of transparency tools to strengthen their policies, processes and performance.