Transparency in clinical trails has become a hot topic after the controversy over Roche's decision not to release full clinical data for its influenza drug Tamiflu after questions were raised about the medicine's efficacy.
Roche sold enormous quantities of Tamiflu to national governments during the swine flu epidemic, and there have been concerns that whether this could have been a waste of money if the drug's effectiveness has been overstated.
Soon a campaign calling for governments, regulators and research bodies to ensure all clinical trial results are published in full has gained heavyweight backing from the health and scientific community.
The project, called www.alltrials. net, a collaborative effort of an unusual group of organizations won support from a number of prominent bodies, including the UK's Medical Research Council (MRC), the German cost-effectiveness body IQWiG and research group the Cochrane Collaboration, and comes with the slogan “all trials registered, all results reported”.
It was set up by a group including Bad Pharma author and GP Dr Ben Goldacre, campaign group Sense About Science, the British Medical Journal (BMJ) and Oxford's University's Centre for Evidence-based Medicine following a series of high profile stories about clinical trial transparency during 2012.
The controversy over Roche's decision not to release full clinical data for Tamiflu led to a meeting hosted by the European Medicines Agency (EMA) and attended by Dr Goldacre among others in November last year to discuss the present situation, where Hans-Georg Eichler, the EMA's senior medical officer, said that the move towards transparency "is irreversible”.
An EMA report followed, reiterating this view, although it also considered that the exact way this can be done is still to be determined – something that is also an area of concern for the European Federation of Pharmaceutical Industries and Associations (EFPIA).
Roche has since said it is open to the idea of talking with one if its biggest critics, the Cochrane Collaboration, about setting up a multi-party advisory board, including experts from academia and industry, to review all the data behind Tamiflu.
Specific demands include:
- The publication of all results for all trials conducted – both past and future – on all treatments currently being used
- Competent legislation and regulations, with robust penalties and incentives, to ensure that this requirement is met
- All universities, ethics committees and medical bodies to recognise that under-reporting of trials is misconduct, and to police their own members to ensure compliance.
The profile of the campaign helped by prominent supporter such as IQWiG states on the AllTrials.net website: “During the past years we have experienced that full availability of all clinical trials and all information on methods and results of these trials is essential for us to provide unbiased and meaningful assessments.
“Health technology assessment should be based on a full evidence base and thus requires registration and reporting of all trials, regardless of whether they are conducted by industry, academia, governmental organisations or others.”
There are also similar comments from the MRC and Drug and Therapeutics Bulletin, while Dr Fiona Godlee, editor of the BMJ – which announced last year it would no longer publish trials where all data is not available – said: “The evidence that much research goes unreported is overwhelming, putting patients at risk and wasting healthcare resources.”
The “Briefing Notes” that accompanied the introduction of www.alltrials.net stated that many studies have found widespread non-compliance with existing recommendations /requirements for the publication of all trial results. For several years, both the EMA and the FDA have required the registration of clinical trials on a website and the subsequent publication of those trials’ results. Yet, studies published in the BMJ, Annals of Internal Medicine, and the New England Journal of Medicine have all found that researchers have complied with those requirements in only half to two-thirds of the cases.
The groups supporting the release of more data are critical not only of the drug industry but also of universities, ethics committees, and medical membership bodies for failing to address this long-festering issue. Their concern is not merely academic. Patients around the world have been harmed by the side effects of drugs such as Vioxx, Avandia, and Actos — side effects that many claim the drugs’ developers knew about or should have known about prior to receiving marketing authorization. If the results of every clinical trial of those drugs had been widely disseminated in a timely manner, they may not have been approved, and may not have harmed thousands of patients.
Those clamouring for more transparency of clinical trial results also suggest that physicians are regularly prescribing expensive new drugs that are no more effective than older, less expensive products. Regulators evaluating a new drug only require evidence of its safety and efficacy when compared to a placebo, not to an existing product treating the same condition. Bad Science et al. suggest that drug companies have indeed conducted such comparative studies, but have never released any results that demonstrated only their product’s equivalence — not its superiority. They also charge that studies that fail to demonstrate the utility of a potential new product never see the light of day. Thus, companies are robbing prescribing physicians of the complete picture of their products’ safety and efficacy.
Firms ranging from Astellas to Roche have announced their intentions to disclose more data from all their clinical trials. Undoubtedly, this trend towards more transparency will spread.
Sharing more data could improve the industry’s standing with a public that is skeptical of its motives. It could give physicians a more complete understanding of a new product’s chemical characteristics, and encourage them to better appreciate their most appropriate uses.
However, sharing more data about clinical trials could also make patients less willing to participate in such trials — many of which will be seen to be failures. Doing so could require companies to spend more money to conduct more trials in order to build a larger mountain of data supporting their products’ safety and efficacy.
Boehringer Ingelheim has become the latest company to say it will publish all scientific data from its clinical trials as the industry continues to feel pressure from open data campaigners.
Speaking at the Germany-based pharma company's annual conference, Boehringer's chair of the board of managing directors Professor Andreas Barner said the move towards transparency was
“irreversible”, although there must be a standard format for trial publication that all companies follow.
“As a company that intensively and successfully conducts research, we will further intensify this exchange in the spirit of greater transparency by publishing all scientific data from all clinical studies for which the company is responsible,” said Prof Barner.
“In addition, we will in future make available to interested scientists all study data – up to the level of anonymised patient data – after the completion of the registration process and also when we have halted development.”
It was a bold move for the company, although it stopped short of joining GlaxoSmithKline in signing up to All Trials, a campaign group for open data that counts IQWIG and NICE among its supporters.
Nevertheless, Prof Barner said that transparency and availability of data was the “right direction” for the industry.
Increasing transparency seems to be the wave of the future. But it remains to be seen whether the benefits of that trend will be as large as its most vocal proponents are claiming, and whether it will have any unintended consequences.