Science and Technology CommitteeWritten evidence submitted by NICE

Introduction

1. We would like to thank the Committee for the opportunity to contribute to this inquiry. In this memorandum we have addressed those matters raised by the committee that relate directly to the work of NICE.

2. The National Institute for Health and Clinical Excellence (NICE) is the independent organisation responsible for providing national guidance on promoting good health and preventing and treating ill health, and from April 2013 our remit will expand to provide a similar service to the social care sector. NICE guidance supports health and social care professionals and others to make sure that the care they provide is of the best possible quality and offers the best value for money.

3. The issue of disclosure of clinical trial data and NICE’s work has been raised in a number of other settings, including with the House of Commons Health Select Committee1 and in published correspondence between NICE’s chairman Sir Mike Rawlins and Dr Fiona Godlee, editor in chief, BMJ.2

4. The issue of public disclosure of clinical trial data is relevant to all our guidance that offers advice to the NHS on clinical practice, but is especially important in two programmes: technology appraisals, which make recommendations to the NHS on the clinical and cost-effectiveness of new and existing medicines and other technologies; and clinical guidelines, which provide advice on clinical- and cost-effective approaches to the management of patients with specific conditions.

The NICE Technology Appraisal Process

5. When NICE appraises technologies such as drugs and medical devices, we ask the manufacturer to provide us with any data, including any unpublished studies they may have, which relate to the appraisal3. We also carry out our own review of the published evidence, including for example examining the European Medical Agency’s European Public Assessment Reports to help secure the information we need.

6. In the case of pharmaceuticals, the medical director of the company is required to confirm that, to their knowledge, the company has provided us with all the relevant information they hold, but as we have no means of independently corroborating this it is impossible for us to know, absolutely, that we have all the unpublished information that might be available. However, we would not continue an appraisal knowing that data likely to be material to the outcome of the appraisal existed but had not been made available.

The NICE Clinical Guideline Development Process

7. NICE’s clinical guidelines are different from NICE technology appraisals in that they provide recommendations across the care pathway for a disease or condition, rather than specifically on a technology or group of technologies.

8. This broader approach means that we do not have the ability to contact every manufacturer of every drug available for a specific condition, so we rely heavily on published evidence. The issue of publication bias, and the non-reporting of negative results, has an additional impact for our clinical guidelines because we would not wish to recommend treatments that are ineffective, instead support the use of those that are clinically and cost effective. If the evidence of lack of effectiveness isn’t published, it makes these “do not do” recommendations4 impossible to compile.

9. This has not been a general problem in guidelines we have published, but it can occasionally make the development of a guideline more challenging. For example, in 2005 we published a guideline on depression in children and young people. In order to produce recommendations on the use of selective serotonin reuptake inhibitors (SSRIs) in childhood depression we wrote to the manufacturers requesting information. We were unable to obtain sufficient information from them on studies that had been carried out, and it was only when the Medicines and Healthcare products Regulatory Agency (MHRA) Commission on Human Medicines published the results of all of the clinical trials they knew about, we were able to develop recommendations on the appropriate use of SSRIs in children. A Lancet article5 describes this in more detail.

Questions Posed by the Committee

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?

11. We believe the revisions acknowledge that there have been problems with the directive and its implementation, and are therefore a genuine attempt by the commission to address many of the problems. The Academy of Medical Sciences report “A new pathway for the regulation and governance of health research”6 provides a comprehensive summary of the issues.

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

12. The Health Research Authority (HRA) was only established in December 2011 and as such it is too early to judge its effectiveness. However, we have begun to develop a good relationship with the HRA and we believe it is making good progress, particularly in the areas of merging research ethics approvals and addressing issues around research governance.

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

13. There have been well-publicised examples of where clinical trial data has not been published which has led to adverse consequences for patients and for health systems resources. We strongly believe that companies should make all the data they have available so that that those organisations and individuals with responsibility for developing recommendations, and making treatment decisions, have all the necessary information to hand to help them do so safely and efficiently.

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

14. This is a complex issue and there may not be a simple solution. It is our view that legislation is not the answer, not least because clinical research and drug development is an international endeavour and regulation as a result would need to apply consistently across jurisdictions.

15. We would prefer to see a solution that is based on research ethics approvals. For example ethics committees could refuse permission for further research, and research funders refuse further funding, if the principal investigator has not published results from previous trials. Regulatory authorities could insist on all trials (even if the results are negative) with a drug for any indication, if it has any type of marketing authorisation, being published and publically available within 12 months of completion.

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

16. As we have described above; clinical research is a global endeavour and we don’t know of any other country that has found a suitable solution to this problem.

February 2013

1 www.publications.parliament.uk/pa/cm201213/cmselect/cmhealth/782/78202.htm

2 www.bmj.com/tamiflu/nice

3 See section 4.2, Guide to the methods of technology appraisal, available at www.nice.org.uk/media/B52/A7/TAMethodsGuideUpdatedJune2008.pdf

4 www.nice.org.uk/usingguidance/donotdorecommendations/index.jsp

5 The Lancet—24 April 2004 (Vol. 363, Issue 9418, Pages 1341–1345) available at www.thelancet.com/journals/lancet/article/PIIS0140-6736(04)16043-1/fulltext

6 www.acmedsci.ac.uk/p47prid88.html

Prepared 16th September 2013