The drug safety departments of most pharmaceutical companies have become too burdened with operations to effectively manage risk. A new approach is needed to detect problems earlier, communicate clear benefits, and prevent a risk-averse public from potentially blocking important advances.
So says Sanket Agrawal, chief strategy officer of Irvine, Calif.-based Relsys International. At the moment, safety departments end up placing 80 percent of their focus on single adverse event (AE) management and aggregate reporting, and the remainder on risk and signal management. For instance, over one-third of many companies’ core safety staff currently supports the “non-value-added function” of AE intake. “It could be the other way around, as intended, through a sustained drive to simplify processes, integrate underlying systems, and perhaps even some regulatory assistance.”
Passive monitoring of products is an outdated notion, given the complexity of today’s medical products, says Agrawal. “Some studies show that as few as 1 percent of AEs even get reported by physicians.” Beyond “being a good citizen,” they have no incentive to do so.
By contrast, doctors in the U.K. are required by regulation to report any AE on the first 10,000 prescriptions of a newly released drug, says Agrawal. In Japan, pharmaceutical companies voluntarily pay physicians to track every patient prescribed a new drug for up to a year after its release. New product distribution is also limited to specific providers. The Japanese approach “seems to be more effective than passive reporting in surfacing abnormalities.”
A few years ago, a pharmaceutical company launching a product in Europe limited distribution to providers willing to actively collect patient safety information, says Agrawal. “The company got three times as many quality reports than they would have otherwise.”
Were physicians in the U.S. to become more conscientious about reporting AEs, “the industry would collapse” in a deluge of data. The public needs constant education about the realities of drug development, says Agrawal. Consumers want risk-free products, unrestricted access, and a speedier drug approval process. But they will also litigate if approvals come too fast or products are abused or misused.
Relsys uses the image of an iceberg in its educational efforts with lay people. “No matter how good the science is,” Agrawal says, “when a drug is released we can see only a percentage of the risks. If we want to know everything, it means we would never release a drug.” The message should be that “all drugs are chemicals and come with side effects, known and unknown. Pharmaceutical companies need to communicate the benefits [correlated to price] versus the risks…and let people make informed decisions.”
The focus has been disproportionately on risk, says Agrawal, “which is understandable given the human propensity to weigh risks higher than rewards. For example, direct-to-consumer ads read through a list of risks, leaving consumers confused about the benefits of a product. Clearly, there’s a lot of room for improvement in the educational aspect.”
Companies could also more actively communicate to the public all they do to monitor known and unknown drug risks, says Agrawal. “If you go back any more than five years, you will see that companies are doing much more now, but are not getting credit for their efforts.”
Proactive Surveillance
On the other side, “clinical trials will never expose risks the way real-world usage does,” says Agrawal. More proactive post-marketing surveillance is required. At the moment, communications between product manufacturers and health care providers is “almost a one-way dialogue, focused on getting drugs on a formulary or approved list.”
Growing acceptance of active surveillance is behind the exponential growth in Phase IV clinical studies and the desire to tightly integrate eClinical and safety tools, says Agrawal. Seamless electronic integration has yet to happen, in part because drug development is a multi-departmental, multi-IT-system process at most companies. “Vendors are just starting to offer that capability.” Some vendors are acquiring complementary technology and integrating in-house, while others like Relsys are pushing for a standards-based open integration through “best-of-breed” alliances.
Risk management, from pre-clinical to post-marketing, needs to be a “holistic discipline,” Agrawal says. Technology is needed in such areas as signal management, regulatory communications, and label update tracking. The U.S., which has separate guidances for risk assessment and risk minimization, is philosophically a bit behind Europe.
The FDA is taking steps in the right direction, including its recently announced plans to do a comprehensive assessment of the safety of drugs 18 months after introduction and to collaborate with the Veterans Health Administration to track how real patients fare after taking drugs, says Agrawal. The FDA has also announced its intentions to “take into account some of the recommendations of the IOM [Institute of Medicine]. There are now budget requests for this, to hire additional people at CDER [Center for Drug Evaluation and Research] and acquire new electronic tools [to facilitate reporting and analysis of AEs].”
The FDA stresses that it wants to “use the strength of science” to support its safety monitoring work, says Agrawal. The agency probably doesn’t have the infrastructure to independently conduct research, as it once did. More likely, the FDA will be “a more active participant in clinical trials” and “make public all clinical trial results,” as is currently being pushed in Congress.
Agrawal’s “holy grail” is to find signals, in real time, directly from physicians’ medical records. “Healthcare systems have the data in a structured format,” he says, but privacy concerns remain a critical barrier.
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