Access to clinical trial information and the stockpiling of Tamiflu
Conclusions and recommendations
On clinical trials
1. We were surprised and concerned to discover that information is routinely withheld from doctors and researchers about the methods and results of clinical trials on treatments currently prescribed in the United Kingdom. This problem has been noted for many years in the professional academic literature, with many promises given, but without adequate action being taken by government, industry or
professional bodies. This now presents a serious problem because the medicines in use today came on to the market—and were therefore researched—over the
preceding decades. None of the latest proposals from regulators or industry
adequately addresses the issue of access to the results of trials from previous years on the medicines in use today.
Recommendation: The Department should take action to ensure that the full methods and results are available to doctors and researchers for all trials on all uses of all treatments currently being prescribed, and should also ensure that there is clear and frequent audit of how much information is available and how much has been withheld.
2. The results of clinical trials on humans are the key evidence used by regulators, researchers and clinicians to assess whether a medicine works and how safe it is.
Medicine manufacturers submit evidence on products they wish to market in the UK
to the Medicines and Healthcare Products Regulatory Agency (MHRA) or the
European Medicines Agency (EMA).
3. The scope for independent scrutiny of a medicine’s effectiveness is undermined by the fact that the full methods and results of many clinical trials are not made available to doctors and researchers. The problem of non-publication of clinical trial results has been known since the mid-1980s. We also heard evidence that trials with positive results are about twice as likely to be published as trials with negative results. While several clinical trial registries have been established, none covers all clinical trials on all uses of all treatments currently being prescribed worldwide. There have been recent announcements by the EMA, and some manufacturers, to improve access to information about clinical trials but none adequately addresses the issue of incomplete disclosure throughout medicine. Opening up information about all clinical trials to medical researchers would support the work of regulators by permitting thorough, independent external review by doctors and researchers .
Recommendation: The Department and the MHRA should ensure, both
prospectively and retrospectively, that clinical trials are registered on an
appropriate registry and that the full methods and results of all trials should be
available for wider independent scrutiny, beyond the work undertaken by
regulators during the licensing process.
4. NICE and the MHRA do not routinely share information provided by
manufacturers during the process for licensing medicines. When applying for a
licence, manufacturers have a legal obligation to provide all the information on the
safety and efficacy of a medicine that is required by European regulators. However,
NICE does not have statutory powers to demand information from manufacturers,
in contrast to the Institute for Quality and Efficiency in Healthcare in Germany, which performs a similar role to NICE. NICE seeks confirmation from the medicine manufacturer’s UK medical director on the completeness of information, but this may not include all clinical trials in other parts of the world, not least because UK medical directors may themselves not have full information. The MHRA confirmed there was no legal obstacle that would prevent it from sharing information with NICE. However, there is no routine sharing of the information provided by manufacturers to regulators as part of the licensing process with NICE. This leads to the risk of omissions and duplication in the collection of evidence.
Recommendation: NICE should ensure that it obtains full methods and results on all trials for all treatments which it reviews, including clinical study reports where necessary; make all this information available to the medical and academic community for independent scrutiny; and routinely audit the completeness of this information. NICE and the MHRA should put in place a formal information-sharing agreement to ensure when NICE appraises medicines it has access to all of the information provided to regulators by the manufacturer during the licensing process.