Not for the first time, the ombudsman for the European Union, Emily O’Reilly, issued a statement calling on the European Medicines Agency (EMA) and AbbVie to cease the withholding of trial data for blockbuster drug, Humira (adalimumab). The company took the EMA to court in 2013 to prevent the publication of data, but reached a compromise, of sorts, whereby redacted documents could be released.
O’Reilly says: “In the case of the remaining redactions of concern to me, EMA has sought to justify them on grounds of commercial interests. I am asking the EMA to reconsider.” In terms of commercial interests, there may be 14 billion reasons why AbbVie aren’t quite prepared for this data to become available just yet.
With the pharmaceutical industry under ever-increasing scrutiny, a topic that is particularly under the spotlight in pharma is the issue of transparency in clinical trials. The AbbVie situation is by no means the only example of the delicate balancing act between protecting commercial interests and providing a full transparent set of clinical trial data. There has been a concerted move towards the latter in recent years, both in the court of public opinion and from the regulatory perspective.
The issues for pharma
The withholding of clinical trial data is a major topic of conversation within the healthcare sphere. For many outside the industry, the topic is clear cut. Last year, World Health Organization assistant-director, Marie-Paule Kieny, said: “Failure to publicly disclose trial results engenders misinformation, leading to skewed priorities for both R&D and public health interventions. It creates indirect costs for public and private entities, including patients themselves, who pay for suboptimal or harmful treatments.”
When Roche’s Tamiflu (oseltamivir) medication began to be stockpiled by the UK government, there was outrage after a Public Accounts Committee report highlighted just how damaging the withholding of trial results on the drug could be. Richard Bacon MP said at the time: “The full results of clinical trials are being routinely and legally withheld from doctors and researchers by the manufacturers of medicines. The lack of transparency of clinical trial information on this drug to the wider research community is preventing proper discussion… We are disturbed by claims that regulators do not have access to all the available information.”
In short, it is a matter of ethics. Patients will ultimately benefit from the full disclosure of clinical trials, so publishing this data is seen as the ethical thing to do.
In recent years, advocacy groups such as Ben Goldacre’s AllTrials have featured heavily in these debates, calling on pharma companies to take the lead and publish data from all of their trials. While a staunch critic of the industry in general (he did, after all, write a book called Bad Pharma: How drug companies mislead doctors and harm patients), Goldacre’s criticisms have gained such notoriety that pharma had to be seen to be taking a proactive approach to becoming more transparent in clinical trial publishing.
Transparency is certainly high on the agenda of the Association of the British Pharmaceutical Industry (ABPI). The body recently launched Disclosure UK, a database that will list the details of payments made to doctors, nurses and pharmacists, as well as other health professionals and healthcare organisations in the UK. Furthermore, transparency in clinical trials has been a key focus for them for quite a while now. In recent years, they have launched a toolkit of practical guidelines towards a standard operating procedure for pharmaceutical companies in clinical trials disclosure.
Pointing to the progress that has been made year-on-year in terms of disclosure, ABPI executive director of research, medical and innovation, Dr Virginia Acha, says: “Our study in the peer-review journal Current Medical Research and Opinion [shows] that transparency amongst industry-sponsored clinical trials continues to improve, with results of 90% of trials on all new medicines approved by the European Medicines Agency in 2012 disclosed within a 12-month timeframe… indicating that the pharmaceutical industry is achieving disclosure in a timely manner more consistently than ever before.”
While that data may be several years old now, the figures from academia and industry make for conflicting reading on the matter of trial transparency. A 2013 study from researchers at Paris Descartes University found that only 50% of clinical trial results make it to print. American physician Christopher Jones pointed out: “The disparity in publication rates between efficacy results and adverse events is particularly striking, as clearly both pieces of information are needed in order to allow clinicians to judge the risks and benefits of a given intervention.”
The international nature of pharma does indeed create a problem in terms of transparency, and this is something that the ABPI highlights as needing more work within the industry. Dr Acha adds: “We do acknowledge, however, that there is more work to do and, alongside our European and international counterparts, we will continue to work with companies towards greater transparency across the industry globally.”
Making things perfectly clear
Online transparency has been a key area where pharmaceutical companies have begun to step up their efforts in this manner. The clinicaltrials.gov website is obviously a valuable resource in this regard. Maintained in conjunction with the National Institutes of Health in the US, it is designed to allow easy access to information on publicly and privately supported clinical studies on a wide range of diseases and conditions.
Some pharmaceutical companies go even further, with their own bespoke websites where users can browse a database of trials sponsored by that company and view the status of ongoing and completed trials. A very impressive entry in this regard is Japanese firm, Takeda. On the website, takedaclinicaltrials.com, the company indicates that “[Our] commitment to transparency reflects our strong support for sharing clinical trial information to benefit patients and to foster scientific discovery in a way that maintains patient privacy and preserves the integrity of our research.”
The site, itself, is well-designed and responsive, providing easy access to the information sought. It is quite a good example of the direction that pharma as a whole should, and is, taking on the issue of transparency going forward. With Novartis, Roche and Janssen, among others, all providing similar portals, it is clear that the pharmaceutical industry is moving in the same direction.
When approached for this article, a GSK spokesperson echoed these sentiments. They say: “Providing researchers with access to data from clinical trials is scientifically essential and helps ensure that the contribution made by volunteers who participate in our clinical trials is used to maximum effect in furthering knowledge.
“At GSK we recognise the importance of publicly disclosing findings from our research and in recent years have made a number of commitments to share information from our clinical trials. This includes sharing all our trial results, regardless of whether they’re positive or negative, and being the first company to establish an online system for sharing with researchers the detailed patient-level data that lies behind our results.”
On transparency, it seems like pharma is certainly moving in the right direction.
**Brexit – an opportunity for change or an opportunity missed? **
In the UK, the life sciences industry has been left reeling by the vote to leave the EU. Before the referendum, many within the industry were very vocal in their support to remain in Europe. One particular quote from ABPI chief executive, Mike Thompson, was of interest: “We know the old Clinical Trials Directive did not function effectively – yet the new clinical trials system will cut the bureaucracy of the old Directive, and not only enable more much-needed research, but will also underpin the EU as the home for clinical trials at global level. By voting to leave, UK trials could face delay, as companies would deprioritise Britain for a more collaborative and harmonised approach available inside the EU.”
As we know now, the decision to leave the EU will leave pharmaceutical regulation in the UK at a crossroads. The European Medicines Agency will surely leave its Canary Wharf home and, with it, take its regulations which apply to the UK. With transparency a core part of the new Clinical Trial Directive, Britain may now lose out on having a key part of the new EudraCT online database, a similar project to clinicaltrials.gov in the US.
On the other hand, the UK will now have to navigate its own murky waters of regulation once Article 50 is triggered. Will it closely follow the EU in its own transparency guidelines, or will the lawmakers take their own separate direction on the matter? As with most things concerning Brexit at the moment, uncertainty is the only surety on the matter. Developments in this area, and across pharma regulation, will be fascinating going forward.
The next steps
To put it very simply, pharma is an industry and, within this industry, there are businesses who seek profit. For those profits to be made, however, people who suffer from ill health must get effective treatment. When pharma is seen to withhold certain data, or choose not to publish them, it reinforces certain negative connotations against the industry and leaves itself open to critics such as Goldacre. There are enough examples over the years of drugs pulled from the market for being unsafe and causing unacceptable adverse effects.
That’s why it is so damaging for the industry, as a whole, to have this perception of keeping data to itself to the detriment of patients. In this era of widely available information, pharma must continue to step up in order to show that all of the information on the medicines we take are made available to critically examine and judge appropriately. We need to be able to ask the question of “if a drug doesn’t work as well in a certain manner, then why?” rather than presenting results that show the drug in a better light to woo regulators and charm investors.
The right sentiments and rhetoric are fine, but it is following through on these that are of most importance. Pharma certainly seems to have got the message. It’ll just remain a matter of balancing this along with their other aims going forward.
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