Science and Technology CommitteeWritten evidence submitted by the National Institute for Health Research (NIHR) Evaluation, Trials and Studies Coordinating Centre

1. Do the European Commission’s proposed revisions to the Clinical Trials Directive address the main barriers to conducting clinical trials in the UK and EU?

1.1 The proposed EU regulation on clinical trials represents a substantial and important change from the current regulatory framework. The changes proposed address important issues required to increase clinical research activity within the NHS, and so deliver evidence and information of importance to patients, public, NHS and wider government.

1.2 Overall the revisions proposed appear to be line with the required amendments identified by several key bodies and organisations. The proposal for a simpler authorisation procedure, a more risk proportionate approach for lower risk trials, establishment of co-sponsorship model, simpler safety reporting, informed consent arrangements for trials in emergency situations, and consolidation of rules for the manufacturing, importing and labelling of medicinal products should all help improve clinical trial conduct.

1.3 There are other barriers/areas of concern for the conduct of trials in the UK which are not covered by the EU regulations. Some of these are related to the interpretation and implementation of regulatory and legislative requirements, and these will need to be addressed centrally by organisations such as the HRA and MHRA. In addition the implications of additional legislation in areas such as data protection need to be considered for research more generally.

2. What is the role of the Health Research Authority (HRA) in relation to clinical trials and how effective has it been to date?

2.1 The HRA is part of a wider network of bodies, including the MHRA and NIHR, working together to try and improve and unify the research approvals process. It is hoped that this activity will lead to the delivery of some key legal requirements to permit clinical trial conduct in a quicker, more streamlined manner. This includes activity to promote proportionate standards for compliance and inspection within a consistent national system of research governance.

2.2 The HRA is still establishing itself but has begun to make important improvements to the current ethical approval processes which will hopefully deliver results quicker. In addition proposals to develop opportunities for information sharing and reporting could deliver important results in terms of reduced bureaucracy and improved transparency. The HRA has been making important connections with key partners and has already established effective working relationships and collaborative activity. However it remains unclear as to the extent of the influence the HRA can have on activity and practice across the NHS, given the current legal arrangements with NHS Trusts being independent legal entities.

3. What evidence is there that pharmaceutical companies withhold clinical data and what impact does this have on public health?

3.1 We have no comments or evidence to be considered.

4. How could the occurrence and results of clinical trials be made more open to scrutiny? Who should be responsible?

4.1 Research funders have a responsibility to produce the knowledge from the research and ensure that it is in the public domain. This serves a number of purposes including: transparency of public money spent, assurance of the validity of the work, patient safety (through publication of negative results), information sharing and engagement.

4.2 There is an increasing focus on the results of research being published. Studies from different countries repeatedly show a 40–50% publication rate, and the recent BMJ article by Chalmers, Glasziou and Godlee “All trials must be registered and the results published”, reported that only around half of all registered trials have published at least some of their results1).

4.3 The DH/NIHR is a partner in the European version of PubMedCentral—Europe PMC. On the NIHR website there is a statement that the DH and NIHR support the principles that:

Ideas and knowledge derived from publicly funded research must be made available and accessible for public use, interrogation and scrutiny as widely, rapidly and effectively as possible.

Published research outputs must be subject to rigorous quality assurance through effective peer review mechanisms.

The models and mechanisms for publication and access to research results must be both efficient and cost effective in the use of public funds.

The outputs from current and future research should be preserved and remain accessible for future generations.

4.4 The standard NIHR contract enables enforcement of many key mechanisms that ensure transparency and openness of clinical trial data. In particular funded researchers must undertake compulsory trial registration before any monetary awards are paid, and in addition they are obligated the release of data to the funder on request. A number of NIHR programmes also publish full protocols or summaries on their websites.

4.5 Publication and dissemination of trial results are also included within the standard NIHR contract which states; “The Contractor shall ensure that the outcome of the Research is prepared for publication in a suitable peer-reviewed journal”. Despite this, the rate of publication from NIHR-funded research is varied, ranging from some research programmes and projects which do not publish their findings to others with a publication vehicle through the NIHR Journals Library.

4.6 NIHR-funded researchers are actively encouraged to submit articles of their research findings to peer-reviewed journals, however this does not guarantee publication for all results through this route.

4.7 In order to address this potential bias in reporting trial results, the NIHR HTA programme achieves near total and complete publication for its research findings (estimated to be in the region of 98%11), whether positive, neutral or negative, through its dedicated journal “Health Technology Assessment”. This process is now being extended to four other NIHR research programmes through the establishment of the NIHR Journals Library. The final reports within the NIHR Journals Library are subject to a full editorial process prior to publication in the relevant journal. It is not until the report meets the quality expected from a journal that it is approved for publication by the editor.

4.8 A current area of NIHR activity is concerned with reducing avoidable waste in research, and an intention to “ensure that all NIHR funded research is published” is a central part of this.

5. Can lessons about transparency and disclosure of clinical data be learned from other countries?

5.1 We have no comments or evidence to be considered.

Declaration of Interests

The NIHR Evaluation, Trials and Studies Coordinating Centre (NETSCC), based at the University of Southampton, manages evaluation research programmes and activities for the National Institute for Health Research (NIHR), and plays an important role in improving the health and wealth of the nation through research. NETSCC has been contracted by the Department of Health to manage evaluation research programmes and activities primarily as part of the research work strand of the NIHR. The NETSCC managed NIHR funding programmes have a national and international reputation for high-quality research and research management.

February 2013

1 Chalmers I, GLasziou P, Godlee F. All trials must be registered and the results published. BMJ. 2013; 346:f105

Prepared 16th September 2013