Disclosure and Drug Research
By Wendy Mensch and Avery Hudson
This is the dawning of the age of transparency. The technological ability to disseminate information has been accompanied by continually increasing public demand for information, and its craving to receive it faster and in more detail than ever before.
No industry is feeling the heat more strongly than the pharmaceutical industry, under pressure from a global consortium of editors and publishers of leading medical journals, heads of medical associations and scientific organizations, government officials, and public interest groups that have independently issued calls to action that have placed the industry under the microscope. They are calling upon the pharmaceutical industry to openly disclose results of completed and ongoing clinical trials for both investigational and marketed products.
These calls to action have elicited strong responses from the pharmaceutical and biotechnology industries, sponsors of clinical trials, and the public. Some drug companies have already launched websites on which they are posting or promising to post the clinical data about their products. The trade organization PhRMA has launched a website that offers members a place to post data without creating individual sites of their own.
Legislation has been introduced in Congress that, if passed, would mandate the creation of similar websites by pharmaceutical companies. In widely publicized testimony at a U.S. Senate hearing last November, Food and Drug Administration (FDA) epidemiologist David Graham singled out five drugs as having serious safety concerns: the acne drug Accutane, the anti-cholesterol drug Crestor, the pain medication Bextra, the obesity drug Meridia, and the asthma drug Serevent.
More broadly, Graham charged that the FDA was “virtually incapable of protecting America” from unsafe drugs. At the writing of this article, the FDA had announced formation of a controversial Drug Safety Oversight Board, whose role it will be to advise the agency on drug complications and warn healthcare providers and patients about safety issues.
What does “transparency” really mean?
What does “transparency” mean when we apply the concept to healthcare?
It may help to think about our own need to be informed about the risks and benefits of treatments. Today, consumers and many health care professionals rely to varying degrees on the media to keep up with useful and important clinical research.
At Ruder·Finn HealthCare, we work to bring medical news to the public on behalf of our clients, often working with medical journalists. These journalists must be highly selective as they look for the clinical research that will be most useful to their readers. Now think of someone with a life-threatening illness, for which there is no effective treatment. More and more people with such “hopeless” conditions are taking advantage of the best existing therapies with the aim of meeting a very practical goal—prolonging their lives until clinical research can expand their options beyond those that existed at the time of their first diagnosis.
The U.S. government recognized the importance of access to clinical trials for people with life-threatening illnesses when it launched ClinicalTrials.gov in 1997 and required all investigators who receive federal funds to post details about their trials and how to enroll.
Even if we don’t have a life-threatening illness, but are thinking about taking any medicine—a pain reliever, for example— it’s good to have current and accurate information about risks and benefits before we decide to pop that pill, or give it to our child.
This March, the Republican Senate Finance Committee Chair and three Democratic legislators introduced legislation that would require pharmaceutical and medical device companies to post results of clinical trials and potential side effects of their products on a public website.
The law would apply to all research, all treatments, all diseases. It would also come with a stiff enforcement measure— a $10,000 daily fine for failure to comply. How can we begin to think about such a potentiality, balancing our professional roles with our personal roles as healthcare decision makers? We can start by thinking about our dual responsibilities to protect and advance the free flow of accurate and truthful information while safeguarding our clients’ confidential information.
When do raw data from clinical research and post-marketing surveillance become information that is of potential use to patients and their doctors —news that we are obligated to disclose? For the past several decades, the threshold between data and clinical practice has been guarded by peer review.
Peer review itself is evolving, as new groups such as the Public Library of Science arise to publish research findings in open-access online journals to complement traditional publication by medical societies and journals and increasingly made available through the National Library of Medicine’s PubMed and other public databases.
The ability of the scientific community to review and publish clinical data—to edit data into clinically useful information— is expanding rapidly. The science concerned with the benefit and risk of drugs in clinical use is called pharmacoepidemiology.To uncover and evaluate safety issues, pharmacoepidemiologists use specialized statistical tools to analyze patient records from clinical trial databases and those of healthcare providers and payors.
The United Kingdom currently has the largest postmarketing research database, based on records in its nationalized healthcare system. In the United States, such records are collected in separate databases by many different organizations.
Integrating these records into a single resource for analysis is a major challenge, and one for which there has not been a surplus of funds. However, efforts are under way to create such a database in specific areas, beginning with cardiovascular disease, with funding from the National Institutes of Health.
As these databases grow and the scientific community becomes more expert in their use, one can realistically envision competently reviewed, complete, understandable information from Phase I through Phase III clinical trials and postmarketing safety being made freely available to healthcare decision makers in an understandable form. If we begin now to envision these possibilities, we can begin to counsel our clients about managing the potential risks and benefits of transparency.
“Altruism and trust lie at the heart of research on human subjects.” Thus begins the statement recently issued by the International Committee of Medical Journal Editors calling for clinical trial registration. It is up to regulatory authorities, industry executives, researchers, and pharmaceutical PR practitioners alike to demonstrate that this observation is, in fact, true.
Providing transparency is one way to illustrate the good intentions of the pharmaceutical industry and may even be a step toward improving the somewhat tarnished image of the industry. But it must be done responsibly, without raising false hope or instilling unnecessary fear. That is why the pharmaceutical industry must not be too rash in responding to the recent calls for action, why it is critical to find a way to provide appropriate information in the right way, at the right time, to the right audiences.
It is in the best interest of drug companies to be open and honest about the results of research they are doing, providing prompt disclosure of the results of post-marketing surveillance, including the adverse events reported with use of their products. Are all clinical trials created equal? Should there be uniform guidelines for disclosure of results for studies in all phases of drug development? For lifesaving drugs, as compared with lifestyle drugs? At what point do reports of an adverse event become serious or important enough to merit public disclosure? Is it when there is one report of a serious side effect? Two? Or not until a statistically significant percentage of patients have experienced that side effect? What if the drug can be lifesaving for some patients, but causes a serious side effect in others?
There is no question that consumers have a right, and a need, to know all there is to know about the drugs they and their family members are taking. But they also need to understand the risk and responsibility that accompany such knowledge. The risk that publicizing positive results of an early stage clinical trial before there is time for them to be fully analyzed, or confirmed by a second study, might raise false hope among a group of critically ill patients.
The risk that news about potential carcinogenic effects of a popular arthritis drug might lead thousands of patients to halt treatment, even though there is no proof of a causal relationship. The risk that one poorly designed study could yield inaccurate results that have the potential to destroy a brand, and with it, perhaps even a small company.
These are all hypothetical but realistic situations for which there is no easy answer. But one thing is certain: Open disclosure of clinical trial results is the way of the future. Proactively addressing the risks and benefits of such disclosure—before it is mandated by legislation—will enable pharmaceutical companies, with the help of their public relations partners, to enter the age of transparency without tripping over avoidable adverse effects. Websites noted in this article:
Clinical Study Results Database (PhRMA)
PubMed (National Library of Medicine)
ClinicalTrials.gov (National Institutes of Health)