Raising the Bar on Transparency

In the highly regulated, multi-billon dollar pharmaceutical industry, transparency can be a delicate, controversial – and often dodged – topic. Pharma’s lowest moments have often come as a result of a lack of transparency.

The recent $4.85 billion settlement that Merck agreed to in order to cover the thousands of lawsuits stemming from the blockbuster painkiller Vioxx – which was pulled from the market in 2004 after clinical trial data indicated it raised the risk of heart attacks and strokes – serves as a reminder of the repercussions of monetary losses, reputational damage, and most importantly, human life, when information isn’t fully disclosed.

Add to that the recent ruling that GlaxoSmithKline’s diabetes drug Avandia must now carry a black box warning after studies indicated that it significantly increased the risk of heart attack in some patients – after it was prescribed to more than 7 million people over the last seven years. Instances such as these, where associated risks aren’t communicated properly or lengthy litigation ensues after lives are lost, only heighten the public’s mistrust of the industry and continue to underscore the importance of transparency, especially in the arena of clinical data.

One pharma company in particular has led the industry with its proactive approach to championing transparency, based on the belief that medical data is one of its most important commodities. “Medical data is what informs patients and prescribers about our medicines,” Eli Lilly Chief Medical Officer, Alan Breier, says. “The higher the quality of the medical information, the more useful our medicines become. I can’t underscore too much the importance of medical information for the success of our business model, the success of our company and the success of the industry.”

Knowing that information that lacks credibility or is pulled from poorly designed clinical trials is a recipe for disaster in pharma, Lilly’s transparency agenda was designed to reinforce and bolster credibility and trust in their clinical trial information. “If medical data derived from clinical trials is of inferior quality, then the entire business model is threatened,” Breier says. “It is absolutely imperative that the medical data that accompanies our medicines is highly credible and trusted.”

Lilly’s transparency path
Acknowledging that transparency was one of the key approaches for increasing credibility and trust, Lilly knew that delivering all available information in a rigorous and objective format to patients, prescribers and payers would increase the likelihood that the data would be trusted and acted upon. With access to positive data, negative data and even inconsequential data, the end user could make fully informed decisions based on a complete understanding of the information supporting the medicines.

With this notion in mind, Lilly began having discussions around clinical trial information transparency back in 2003, when it was determined that transparency was in fact consistent with the company brand. “We felt that bringing more transparencies to clinical trial information would be very useful and important,” Breier says. “We’re a highly science-oriented company, a very innovative company, and free and objective disclosure of information is very consistent with that scientific mission so it was quite compatible with who we were.”

Not only did providing a greater level of transparency seem consistent with the company but it was projected to be useful and valuable to the overall health community, and so
Lilly decided to launch a clinical trial registry. It was a bold step, since at the time there were no clinical registries in the industry and in fact, releasing full clinical trial information to the public was still considered somewhat taboo.

When the registry went live in 2004, there was virtually no clinical trial information available on the web. “We were the first to initiate one voluntarily – we thought that not only could we do service to patients, prescribers and payers related to our own medicines, but perhaps play a leadership role in the industry and academia by moving forward with transparency around our clinical data,” Breier says.

Knowing a variety of users would be accessing clinical trial information – from patients to physicians to payers – the publicly available, online registry was designed in a user-friendly format, complete with a glossary of definitions, clear guidelines and defined time commitments. As part of the registry guidelines, Lilly discloses clinical trial results for phase I, II and III studies when a drug’s indication is approved and it is commercially available.

The utilitarian aspect of the registry is an important component for helping to build trust and credibility in Eli Lilly medicines. The objective, accessible format makes it easy for all stakeholders to make more informed decisions: when contemplating a treatment, patients can utilize the registry to see all available information on side effects and safety data; physicians can understand all the different aspects of data before making prescribing decisions; payers can use data to apply to issues of access and reimbursement.

“On the one hand, it increases the trust and credibility but it also provides a very useful service for patients, doctors, prescribers and payers in that they can now go to the clinical trial registry and all the information we have on our marketed drugs is contained in one place,” Breier remarks. “There will be better appreciations of the nuances of the data and of what a patient is likely to experience because more data is available, so that has the potential for essentially enhancing patient care.”

Ripple effects
Lilly’s launch of its clinical trial registry, the first of its kind in the industry, not only has enabled Lilly to communicate more directly with those who use Eli Lilly medicines but it has also helped to alter the industry landscape towards greater levels of transparency.

“I think we debunked some myths around transparency as well,” Breier acknowledges. “I think there were historic concerns around putting too much information out into the public domain and we’ve shown that by actually putting forward substantial amounts of information, you increase confidence in your molecules and you strengthen your product and company brand.”

Since that time, clinical trial registries have become common practice and most companies in the pharma industry have committed to posting clinical trial data. Pfizer has even gone so far as to post its R&D pipeline online – where you can track the progress of phase I, II and III candidates, listed by compound name, therapeutic area and indication.

Lilly’s move has also spurred activity in the academia and regulatory community arenas, with legislation around clinical trial registry requirements – The Federal Drug Administration Authorization Act – having recently passed the House. Among other global medical and healthcare organizations, Lilly has also adopted clinical trial registration standards proposed by the World Health Organization (the WHO Technical Consultation of Clinical Trials Registration Standards) in April of 2005 to provide transparency and accountability of clinical trial research.

Breier anticipates even more legislation impacting the industry in the near future. “There’s going to be a lot of fast-moving pieces occurring over the next six to eight months as the federal legislation takes hold and the use of clinicaltrials.gov is expanded. It’s all towards greater degrees of access to information and transparency, which ultimately is good for the healthcare system.”

But Lilly isn’t one to be reactive – and is taking improvements into their own hands. With a clinical trial registry team working full time on the registry and target dates set upon which clinical trial results will be posted, Lilly is doing its own legwork to promote greater transparency. Of course, changes and pressures from the external environment are constantly monitored and Lilly also works to evolve its approach to meet those.

“We’re continuing to adapt to the external environment: there are new regulations coming from the federal government, journal editors have put forward different kinds of requests for clinical trial postings, and different states across the country have put forward their own requests,” Breier expands. “There’s a variety of streamlining and improving the actual production of the clinical trial registry that has occurred over time.”

Lilly has even gone so far as to bring in an external auditing firm who they gave complete access to their clinical trial registry to do an external audit. Reports of the audit were published on Lilly’s registry as well as the auditing firm’s site, which highlights the useful role that auditing plays in the importance of authenticating information on the web.

New avenue of transparency
Lilly has recently led the industry again in the transparency realm by being the first to apply its transparency model around its clinical trial data registry to the area of educational grants, with the recent launch of a grant registry.

“We felt that greater transparency around our educational grants, grants that primarily support continued medical education (CME), would also be very important so we launched the first of its kind in the industry,” Breier explains.

Launched May 1, 2007, the grant registry posts online all information related to educational grant funding and other monetary contributions provided to US-based organizations – including medial societies, academic centers, patient groups and nonprofit institutions. The registry contains names of every organization in the US receiving funding from Lilly, beginning in the first quarter of 2007, along with the amount and description of the intended use of funds. Information is updated on a quarterly basis to reflect the latest funding and recipients.

The move allows the public to see how grants are being provided and used, so as to answer any questions related to the nature of relationships between Lilly and the organizations it supports. Educational grants are typically focused on the therapeutic areas where Lilly has particular scientific and drug development expertise (such as endocrinology, neuroscience and oncology) and are provided to enhance patient care, improve the healthcare system and help organizations inform and empower healthcare professionals and patients.

Lilly’s move to make a grant registry publicly available is already receiving nods of approval from across the industry. “It was very widely and positively received on the Hill in Congress because there had been concerns around transparency on this topic. This has also prompted other companies to indicate that they will also be putting forward grant registries.”

With other companies already indicating that they will be following suit, Breier predicts the same pattern of transparency around clinical trial data will soon be exercised in the area of educational grants. “Our action is very positively received in Congress and that signals to other pharma companies that by moving forward and being proactive, we can move the agenda in a very positive way, and therefore, the need for legislation is decreased when companies are actually moving forward in a voluntary proactive way.”

While many in the industry continue to learn the importance of transparency the hard way, Eli Lilly and others are continuing to demonstrate the positive implications of proactively committing to transparency – and are helping to shape an improved image of the industry and ultimately, a better healthcare system. “Activities like the clinical trial registry and the grant registry that are focusing on greater amounts of information sharing and transparency ultimately are good for the healthcare system,” Breier acknowledges. “This has been a bit of a revolution leading towards greater and greater degrees of transparency and we’ll see more as we go towards the future.”

About the contributor
 
Alan Breier was named Vice President of Medical and Chief Medical Officer for Eli Lilly and Company in August 2003. He is a member of the LRL policy committee and Lilly’s senior management forum. He joined Lilly as a research fellow for Lilly Research Laboratories, a division of Eli Lilly and Company, in March 1997, the same year he was appointed adjunct professor of psychiatry at Indiana University School of Medicine in Indianapolis. The next year he was named team leader of the Zyprexa product team at Lilly. In 2000, he became adjunct professor of psychiatry at the University of Maryland School of Medicine.