Clinical Trial Transparency – A Personal View
During the time I worked as research, medical and innovation director at the ABPI, between October 2012 and January 2015, there were dramatic changes in the way in which clinical trial transparency was being discussed throughout the R&D ecosystem, resulting in long-awaited improvements.
Thankfully, this time, there will be no turning back.
Since I wrote an opinion piece in Pharmafocus a year ago, I am in a position to stand back, take stock and consider the relative impact of self-regulation, regulation and ‘people power’ as it pertains to clinical trial transparency.
From reading Sir Iain Chalmers’ article, ‘From optimism to disillusion about commitment to transparency in the medico-industrial complex, I saw that my predecessors at the ABPI had sought and received advice from him on how best to deliver on the commitments that the pharmaceutical industry had been making to improve clinical trial transparency. A key piece of advice from that article which I had taken to heart was to put in place mechanisms for promoting and monitoring adherence to industry guidelines.
It was with this advice in mind that I commissioned a toolkit, to support companies to implement industry guidelines and in parallel, I undertook research to assess the rates of disclosure of results of company-sponsored trials associated with new medicines approved in Europe between 2009 and 2011 and in 2012. Research using the same methodology is ongoing for products approved in Europe in 2013, and no doubt this will also be published in due course.
The first publication resulted in a number of companies being found in breach of the ABPI Code of Practice, including one company which was deemed to have “brought discredit upon, and reduced confidence in, the pharmaceutical industry”. In evidence to the House of Commons Science and Technology Committee’s Inquiry into Clinical Trials in 2013, the ABPI also committed to “appoint a third party service provider to monitor compliance with current and future industry codes of practice on clinical trial transparency”.
A compliance audit exercise is also ongoing for products approved in Europe in 2012 and 2013, to ensure that all applicable fields in registries and databases are completed as per WHO’s minimum trial registration data set and IFPMA’s requirements for results disclosure. This initiative will hopefully stand companies in good stead for the requirement to populate the EU Clinical Trial database and to comply with the new EU Clinical Trial Regulation.
The IFPMA’s first joint position paper called for trial registration and reporting of summary results by the global pharmaceutical industry in 2005; however these provisions, in the form of the updated joint position paper of 2009, were not brought into the IFPMA Code until 2012. The ABPI moved to incorporate the IFPMA’s 2005 clinical trial transparency requirements into the ABPI Code of Practice in 2008, but no complaints were heard under the relevant clauses until after the above mentioned research was published in 2013.
In this instance, there appears to have been a structural flaw in self-regulation, as clear ownership and lines of accountability for ensuring system-wide implementation across the global industry were not in evidence. Another factor at play is that trade associations understandably have to balance commercial imperatives such as pricing, reimbursement and market access against intangible considerations such as openness, a balancing act that can be difficult for them to judge correctly at times.
Global industry action
So how did regulators deal with this issue? The FDA moved to mandate the registration and reporting of summary results of applicable trials in clinicaltrials.gov in the FDA Amendment Act of 2007, but has also been criticised for not being proactive in the monitoring of adherence and application of sanctions for non-compliance.
Europe has been playing catch-up but, with the implementation of the new EMA policy and new EU Clinical Trial Regulation, is now poised to overtake the FDA with more stringent requirements, including the posting of Phase I trials in healthy volunteers. The Health Research Authority (HRA) in the UK has pre-empted this and from April 2015, sponsors are required to declare that all trials in active recruitment have been registered at the time of application for approval for a clinical trial. Given that HRA does consider requests for registration deferral for a Phase I healthy volunteer trial when justified, it is disappointing that it now finds itself the subject of a judicial review.
To what extent has all this flurry of regulatory activity been influenced by campaign groups? It may seem that many, if not all of the recent strong statements on clinical trial transparency from several quarters, including the pharmaceutical industry, have been precipitated by the conscience-pricking effect of public campaigns. In raising awareness of the importance of clinical trial transparency, campaign groups such as AllTrials have undoubtedly galvanised disparate organisations including public, private, charitable and regulatory bodies to act decisively.
The campaigners have asked the difficult questions and confronted those who had the power to have changed things for the better before now. Although it was not comfortable, I was happy to be challenged and in turn challenged the member companies within ABPI. In bringing together the campaigners and the research community (in the public and commercial sectors), attempts were made to address thorny issues such as how best to achieve disclosure of the vast number of historic trials on older products. It was unlikely that there was going to be a legal mandate to do this, but appeals on ethical grounds have clearly had some effect. To their credit, the medical, statistical and compliance functions in the companies responded positively and gave their full assistance at such meetings.
Earning patient trust
When I joined the pharmaceutical industry, I was motivated by a desire to help develop treatments which were badly needed for people suffering from diseases such as those caused by HIV and chronic hepatitis C.
Over the last twenty years, there have been great advances in the treatment of these conditions as well as many others, in large measure due to the intellectual and financial capital invested by the pharmaceutical industry, as well as the public and charitable sectors. More than ever, it is recognised that clinical research is a collaborative exercise, requiring more than infrastructure, trained personnel and efficient processes.
Yet goodwill from patients is paramount. The trust of patients and the public must be maintained if we are all to benefit from the fruits of research and development of new medicines. It can only be a good thing that there is greater public and patient involvement in clinical research, which means that in future, ‘people power’ along with self-regulation and regulation can hold the research community to account.
The first company that I worked for was GlaxoWellcome. This was at a time it was leading the way in good publication practice for pharmaceutical companies as described in Sir Iain Chalmers’ article, and things appeared to be moving in the right direction.
However, at times of organisational change momentum is easily lost. It is imperative therefore that the research-based pharmaceutical industry does the right thing, no matter how difficult it is to do in practice. Organisations need to make it easier for individuals at all levels to advocate the right thing. When I joined the ABPI in 2012 and was asked to address the charge that the pharmaceutical industry “still routinely withholds clinical trial data,” what did I do? I checked. I published what I found. Was this easy? No. Was this the right thing to do? Yes.
Bina Rawal is an independent consultant and former research, medical and innovation director at the ABPI
The views expressed in this article are mine alone and should not be ascribed to any other party.
Submitted June 2015.
Roche’s Genentech has announced that the phase 3 ALINA trial assessing Alecensa, compared with platinum-based …
GSK has announced positive results today from its first efficacy trial for Shingrix recombinant zoster …