About CERTs
Annual Report Year 3
Putting Our Heads Together:
Fostering Collaboration
The Risk Series | Parternships to Advance Therapeutics | Outreach
The Risk Series—
“Benefit the Patient; Manage the Risk”
No medical product can be 100% safe or effective. Caregivers, researchers, regulators, and all involved with the administration of healthcare must continually seek a balance between the risks and benefits of therapies as they are developed and used—a concept that has been called “risk management.”
But measuring, communicating, and minimizing these risks is an intricate labyrinth. Currently, these daunting tasks are performed piecemeal, using many different methods in the various geographic, scientific, and therapeutic areas. Unfortunately, little of this critical effort is guided by research aimed at defining the best ways of aggregating appropriate data and applying it to individual patients in practice or communicating it to the public. The result is gaps in our knowledge of risk and benefit as they exist in the everyday, clinical setting. Defining a research agenda that can fill in these missing pieces is the focus of the Risk Series.
The CERTs program continues to work towards improving the balance of benefit and risk across all therapeutics. Calling on its eclectic collaborative resources, the CERTs has teamed with the FDA, the Pharmaceutical Research and Manufacturers of America (PhRMA), and the AHRQ to gather academic researchers, leading physicians, government representatives, leaders from the pharmaceutical industry, and safety advocates from a variety of disciplines and sectors, to conduct the Risk Series. These workshops focus on three key areas:
- Communication: How are the risks of a therapy best communicated to a particular audience? How do the communication needs of the patient differ from the physician or the media?
- Assessment: What are the information gaps in the current system for quantifying a given therapy's risk to the patient? How can the various sectors, i.e. government, academia, business, etc., work together to create a more seamless system?
- Management: Once risk is identified, how do we minimize patient exposure to it? How do we tip the balance towards benefit?
In 2001, the first of these workshops took place to discuss communicating risk to caregivers and their patients. Participants concluded that there is no source of a coordinated view of the system of risk communication. Multiple independent parties are doing their best, but they often lack guidance based on evidence about how to proceed and how to coordinate their efforts. While many intermediate steps were identified, the overwhelming consensus of the participants was that a comprehensive approach to information management is needed. The results of the meeting are currently in review for publication.
The following year saw an even more complex matter being tackled. The Risk Series workshop on risk assessment was held in the spring of 2002 and gathered a who's who of regulatory, industry, academic, and scientific experts.
One of the greatest challenges to accurate risk assessment is the way in which drug safety is primarily monitored today. A chief source of information is the Adverse Event Reporting System (AERS), maintained by the FDA's Center for Drug Education and Research (CDER). This system gathers data on adverse drug reactions submitted either directly by caregivers via the FDA's MedWatch service or through the drug's manufacturer, as mandated by law.
Once the AERS receives enough reports of an adverse event related to a particular therapy, an alarm is sounded and regulatory action is taken to minimize risk. But a reporting system is only as good as the data that it receives. If important adverse events are not reported, or even identified as important in the first place, the AERS cannot be an adequate, standalone catch-all.
The Risk Series workshop on assessment identified the obstacles to gathering more accurate risk data and offered several suggestions on which research questions to pursue. Throughout the meeting, the importance of multi-sector collaboration was made clear repeatedly. Risk information without a clear denominator or common nomenclature has important, but ultimately limited, value.
A particular emphasis in the assessment workshop was on the acceptability of risk. For patients with cancer, a much greater amount of risk is acceptable when taking a potentially life-saving medication than for someone with a common upper respiratory infection taking a prescription antibiotic. But how much risk is acceptable when weighed against a therapy's benefit? How is this quantified?
Public acceptability of the risk inherent to medication use is understudied, though the Risk Series will conduct a workshop on communicating risk to the media and how the media then relays that information. This is a key component that shapes the public's attitude towards the issue. More systematic analyses of acceptability of risk are an urgent need.
Advances in technology must also be harnessed. A nationwide, electronic medical records system could improve therapeutic safety, but is such a system feasible? What other technological innovations, existing or yet to be developed, might reduce risk? These and other high-tech questions became one of the top priorities on the meeting's resulting research agenda.
A relatively simple solution offered by the panelists was requiring that a diagnosis be written on every prescription, greatly reducing the risk of an error at the dispensing stage of therapy use. This one step would also provide a wealth of data for future study of risk.
The results of the risk assessment workshop are being prepared for journal publication, offering the group's conclusions and full recommendations on how to proceed.
The third of the five Risk Series workshops took place in the fall of 2002 and focused on assessing benefit. Once risk is assessed and communicated effectively, how do clinicians and regulators weigh it against the potential benefits of a therapy?
The workshop concluded that research aimed at the marketing approval for medical products often does not provide those who must make therapeutic decisions (patients, doctors, health system and payer administrators) with the information they need concerning the comparative medical outcomes and costs of therapeutic strategies.
Major recommendations of the participants included the formation of a “national problem list” outlining the therapeutic questions considered highest priority from the perspective of public health, the funding of significant research on the way in which information can be presented to improve the correspondence between the values of patients and their medical decisions, and a continued focus on large, simple, post-marketing clinical trials.
Many questions exist about the methodology of assessing benefits, including a variety of statistical and clinical issues. How can we be sure that an apparent difference in treatment effect based on a clinical patient characteristic is real or just the play of chance? How do we interpret apparent differences in treatment effect in different countries? How can supposed surrogate endpoints be validated to allow generalization of short-term findings to broad populations over the long term?
Little funding goes into research to understand medical decision-making. The value of assessing benefits and risks could be greatly enhanced by such research because it will reveal the methods of information presentation and professional interaction that led to the best decisions, providing a model for future endeavors.
Those who make decisions about healthcare at the individual level and those who fund healthcare remain concerned that inadequate empirical data exist on the risks and benefits of many routine therapies. By increasing the number of comparative clinical trials focused on answering questions that drive medical decisions, such as the effects on longevity and quality of life, the balance of benefits and risks can be tipped in the patient's favor.
The fourth Risk Series meeting will examine risk communication and the media. The enormous impact of the media on public perceptions and individual decision-making is obvious and the recent national discussions about anthrax and smallpox vaccines have reinforced the importance of this issue. Yet little research is done to develop an understanding of the implications of local and mass media on specific perceptions of risk and benefit.
This meeting will bring together a small, representative group from the media, academic researchers, government agencies, the medical products industry, and consumers. The product of the meeting will be a research agenda that will provide a resource for those interested in communicating broadly about the risks and benefits of proposed therapies and for the press to intensify its efforts at self-examination.
The final Risk Series meeting developed a research agenda concerning the tools available to implement risk management programs. Held in early 2003, the workshop gathered leaders across all sectors to draw the big picture on the state of risk management. The participants brainstormed on a number of key issues:
- The effectiveness of risk management techniques for patients
- The effect of risk management programs on the healthcare system
- The interaction between multiple risk management programs
- The unintended consequences of risk management programs
In March of 2003 the CERTs hosted a “roll out” of the risk management series in which the findings and recommendations of the series were presented to policymakers and the public. At this event, the major concepts of risk management were concisely summarized so that what we already know can be more effectively integrated into policy, regulatory processes, and clinical practice.
Just as importantly, the research agenda emanating from the Risk Series charts the course to a much brighter future in which the best therapy can be offered to each individual person through a well-informed consideration of specific benefits and risks of therapeutic options.
Perhaps the most valuable products of these workshops are the collaborations and research that have already sprung from them. Each of these new projects, like the Risk Series itself, will further explore the assessment, communication, and management of risks associated with therapeutics.