Out in the open

In recent years, the pharmaceutical industry has seen some major changes in the mandatory requirements of clinical trial registration and the public disclosure of results: the introduction of the 2007 FDAAA legislation and, in parallel, the ongoing evolution of the European public disclosure requirements. This article reviews the background to the introduction of this legislation and the impetus for change, and outlines the current reporting requirements. The potential implications arising from these changes and the ongoing need for increasing transparency in the medical communications industry are also discussed.

Pharma has long been under scrutiny, with many concerns  about its funding of clinical research and the potential for bias via suppression of negative data and inflation of positive findings via redundant and duplicate publications.

Many calls ensued for trials to be registered, leading firstly to the FDAMA legislation, which required the registration of efficacy trials in serious and life-threatening diseases and the subsequent inception of the ClinicalTrials.gov register in 1998. Initially, a number of pharmaceutical companies opposed the registration of trials, as reflected in the 2002 guidelines issued by the Pharmaceutical and Research Manufacturer of America (PhRMA). However, this stance was seriously challenged by the policy adopted by the International Committee of Medical Journal editors (ICMJE) in 2004, which outlined their intent only to publish studies that had been prospectively registered. This, together with a series of high-profile industry lawsuits, significantly changed the landscape and perceptions about the need for disclosure, which in turn led to the current disclosure requirements and the widespread industry commitment that we see today.

Current disclosure requirements: FDAAA
The US Food and Drug Administration Amendments Act of 2007 (FDAAA) is the most comprehensive reform of prescription drug regulation in several decades. Now mandatory are the registration and public posting of results for Phase II-IV trials of all FDA-approved medicinal products and also those due to be submitted for marketing approval to the FDA.

All applicable trials must be registered on ClinicalTrials.gov within 21 days of first patient enrolment. The timing requirements for posting of the associated results are dependent upon the status of the product being studied: for unlicensed drugs, trial results must be posted within 30 days of either marketing approval or an issue of non-approval. For licensed medications within licensed indications, posting within 12 months of either the estimated or the actual trial completion date, whichever is earlier.

Transparency: a priority for EMEA
In its Road Map to 2010 and its Transparency Policy, the European Medicines Agency (EMA) made a commitment to increase the level of transparency in product-related activities: strengthening transparency of the European Union Drug Regulating Authorities Clinical Trial (EudraCT) database is outlined as one initiative.

This commitment to transparency was reiterated in this year's draft Road Map to 2015. As a result, more publicly available clinical trial disclosures are anticipated in Europe, with registration information expected online later this year, and results postings in mid-2011.

Implications for medical communications
The increased requirements of clinical trial registration and the subsequent reporting is a clearly an important advancement for pharma. But what does it mean in practice?

Transparency, transparency, transparency
Given the ongoing debate and increased spotlight on disclosure, the need for transparency has become ever clearer. Many companies have now elected to make public their commitment to this process via corporate policy statements. This increased transparency has spread beyond the trial disclosure process – there is now a pressing need to ensure robust operating procedures and standards are in place in the wider dissemination of data as a whole.

Visible and public adherence to ICMJE and other relevant guidelines, such as Good Publication Practice 2 is now considered by many in the field to be mandatory: this is a positive move that will help rebuild public trust in the clinical development process and accompanying communications.

Latif Akintade, VP, global medical affairs, Eisai Inc, explains: "Medical communication needs to be undertaken in a transparent, appropriate and timely fashion consistent with applicable legal, regulatory, industry and ethical standards."

To publish or not to publish?
The medical and allied publishing communities have clearly embraced and, indeed, been strong proponents of the public registration of clinical trials. However, some initial concerns surfaced about whether or not journals would accept results that had been previously posted.

These concerns were allayed by the June 2007 ICMJE update on trial registration which affirmed the group's willingness to consider for publication results that have been previously posted, providing they have been presented in a brief structured abstract or table of less than 500 words. This position was reinforced by a subsequent BMJ editorial, which advocated to other journals the publication of results reported under the law to ClinicalTrials.gov. The peer-review aspects of publication were considered to add value to the clinical development process by enabling further interpretation and validation of data.

The exact impact of the more stringent EMEA disclosure requirements and any subsequent extensions of the FDAAA legislation, in terms of both their commercial and communication implications, remains to be seen. However, in the meantime, it is clear that current disclosure requirements do not change the need or desire for well-founded peer-reviewed publications and the critique, challenge and discussions this process brings.

What may potentially change though, are the timelines associated with publication. For many companies, the public posting of results will necessitate the need for speedier and more widely accessible publication of data from a corporate responsibility and commercial perspective. This in turn may lead to an evolution of the publication process: open access communication channels and databases, together with the exploration of speedier digital dissemination options are likely to become more attractive.

It's all in the planning
All those involved in the clinical development and allied communication disciplines need to respond to this increased rigour and put appropriate procedures in place to ensure that they are compliant with all current and anticipated requirements. In particular, pharma needs to plan appropriately.

John Gonzales, global lead for publications, AstraZeneca explains: "Communication activities must be undertaken in a responsible and ethical manner, taking into account relevant external standards; paramount consideration must be given to ensure that all relevant information is communciated clearly and in a timely way."

Great care must also be taken when estimating trial end dates, given that this, in turn, dictates posting timeline requirements. Aligned to this, companies are increasingly setting their own internal standards and guidelines with regards to acceptable publication timelines following completion of their clinical trials. The pressure associated with this and the concomitant needs in terms of planning, resources and understanding of external information needs are likely to increase as we move forwards.

In summary
The regulatory environment and associated disclosure requirements are evolving, and we are likely to see more changes, complexities and stringent requirements moving forwards. As an industry, we need to embrace these changes, and continue our focus on building trust and ensuring credibility.

The Author
Alice Choi is global head of Complete Medical Communications
She can be contacted at Alice.Choi@complete-mc.com

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