Clear Road Ahead - Pharmaceutical Executive

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Clear Road Ahead
An industry standard for publicizing clinical-trial results is a ways off. But pharma's openness to more transparent procedures is moving things in the right direction.


Pharmaceutical Executive


Lilly has specifically voiced the need for a uniform global standard for posting clinical-trial information to all stakeholders, including academia, industry, WHO, PhRMA, journal editors, and policymakers. From the company's perspective, the alignment of registry requirements in a single database that is accessible through one Web site would be ideal. While the company recognizes that there is a movement toward such a standard, Lilly also sees hurdles on the horizon, such as the lack of a compliance mechanism. Although the disclosure of clinical-trial results is not federally mandated, Lilly has made this disclosure a corporate standard and the company has even committed to utilizing a third party to audit and verify adherence to its standards of disclosure.

In terms of study initiation, all Phase II, III, and IV trials will be posted on Lilly's corporate registry and on an independent public registry site, such as http://www.clinicaltrials.gov/, at the start of each study. At a minimum, the company makes the following information publicly available when a trial begins:

  • unique trial-identification number
  • brief title of the trial
  • trial description in layman's terminology
  • trial phase, type (e.g., interventional), status, and purpose (e.g., treatment, diagnosis, prevention)
  • intervention type (e.g., drug, vaccine)
  • condition or disease
  • key eligibility criteria, including gender and age
  • trial start date and projected end date
  • location of the trial
  • contact information.

Once a trial is completed, Lilly discloses Phase I, II, III, and IV results—regardless of outcome—no later than approval of the drug's first indication and commercial launch. Following the initial approval, results of all other Phase II, III, and IV clinical trials are disclosed within one year of trial completion. The only exception to these disclosure guidelines is when posting to the registry would compromise publication in a peer-reviewed medical journal. For studies that are being considered by peer-reviewed journals that prohibit pre-publication results disclosure, the results will be posted on the registry at the time of publication.

In addition to posting results, Lilly discloses a comprehensive description of the trial design and methodology for each study. The company also goes beyond the publication of raw data to include a summary of results, statistical analyses, safety data, and any peer-reviewed manuscripts that have been published.

GlaxoSmithKline has also been aggressive in making clinical-trial information available through its corporate Web site (ctr.gsk.co.uk/). A link to GSK's registry is easily found on the corporate home page, and the registry includes information about clinical trials completed since the formation of GSK on December 27, 2000. With respect to currently marketed products, GSK is providing summaries of studies completed before that date, if the results are likely to inform medical judgment.

GSK intends to post summaries of pre-marketing trials of new medicines and new formulations of marketed medicines no later than the first launch of the product in a major market. For already-marketed GSK products, the company intends to post summaries of trials as they are completed, analyzed, and written up. It will include pre-marketing trials of new formulations before launch in a major market when these trials provide important safety information that is relevant to marketed formulations.

As with other registries, GSK's provides scientific, non-promotional summaries of clinical-trial results, regardless of whether the results may be viewed as positive or negative. GSK's clinical-trial summaries typically include the following characteristics:

  • study title, rationale, objectives, and phase
  • study design, treatment schedule, and location
  • statistical methods
  • study period
  • study population and demographics
  • results for primary and secondary endpoints defined in the trial protocol
  • adverse events
  • references to publications in medical literature, when publications of individual studies exist; when it has not been possible to publish a clinical trial within one year of posting on the registry, a conclusion is added to the trial summary.

AstraZeneca has a separate Web site dedicated to publishing its results ( http://www.astrazenecaclinicaltrials.com/). On July 1, 2005, the company began registering all of its new clinical trials that satisfy IFPMA's definition of hypothesis-testing. On September 13, 2005, the company began posting the results of all hypothesis-testing clinical trials it sponsors. Basic information on such trials will be posted on its corporate Web site, as well as on clinicaltrials.gov. AstraZeneca has also committed to posting information on any new trial within 21 days of its inception.

Overall, AstraZeneca's registry is extremely comprehensive. The site includes postings of all core safety and efficacy registration trials for medicines approved since the formation of the company on April 6, 1999. It also includes global trials completed since that date, and US trials completed since January 1, 2005 for all currently approved medicines. The company points out that posting results is currently an ongoing process due to the large number of trials, but it plans to have its registry fully up-to-date by the end of 2005.

Genentech, in contrast, does not currently have a corporate site dedicated to registering clinical results, but the company has offered to provide more transparency to its research in accordance with the proposed ICMJE requirements. Protocol information is currently posted at clinicaltrials.gov. Clinical-trial results of Phase II, III, and IV trials for marketed products approved after January 2003 are also to be posted.

In an effort to aid physicians and others in locating the information they need, Genentech has also been proactive in developing two guides: "Browsing Genentech Studies That Are Open for Enrollment" and "Accessing Genentech's Clinical Trial Study Results." Both can be found under the "Pipeline" tab at Genentech's Web site, http://www.gene.com/.

The Registry Debate

With various companies applying somewhat different approaches to publicizing trial results, the biggest challenge has been—and will continue to be—putting standard operating procedures in place. These are necessary to ensure the quality of information and timelines for posting study results and the registration of clinical trials. PhRMA is currently in ongoing discussions with WHO to agree upon the data elements, timing, and protection of certain proprietary information for the registration of clinical trials. A critical challenge here is ensuring that there is a single global standard for these activities. In order to attain this goal, there may be some minor changes to the guidelines.

Several legitimate concerns are being raised by pharma companies regarding some of the proposed clinical-trial registry requirements and expansions.

Interpretation The idea behind trial registries is to allow public and healthcare professionals to draw their own conclusions by publishing data without synopses or interpretations. Many pharmaceutical companies argue that while they are very clearly and prominently posting information on their registry Web sites, the information being provided should not replace the informed medical advice or medical treatments of a healthcare professional. While registries and results databases may reduce bias in reported results, publication of uninterpreted scientific data opens a large window for misinterpretation. How will the public interpret results from similar trials with different outcomes? Without conclusions, how will consumers determine clinically and statistically significant results? How will the average person even understand the data?

Confidentiality One of the key purposes of clinical trials is to evaluate potential products for their effectiveness in treating specific disease states, in hopes of gaining regulatory approval. Maintaining confidentiality of this proprietary information at early stages is critical. Pharma companies' revenues depend on beating competitors to market with new or improved products. If companies are forced to share proprietary information early in the clinical-trial process, they could lose significant competitive advantage. Substantial loss of the financial benefits of innovation could, in turn, deter pharma companies from investing as heavily in drug development.


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