A New Culture of Safety
October 2007
Amidst the ever-increasing public focus on drug safety, the pharmaceutical industry must rethink its approach on how post-marketing research is conducted. As an industry, we know that to get valuable and meaningful safety and outcomes data in a real-world population, we have to conduct studies that involve a large number of patients in natural conditions. Although the industry is skilled at conducting market-driven research, the approaches taken in gathering useful, regulatory-relevant information have fallen short. With this in mind, industry and regulators must work together to ensure that long-term safety data on available drugs is of the highest quality.
The main challenge the industry faces with regard to post-marketing research is learning how best to obtain robust scientific data and clinical information in an efficient and cost-effective manner. Pharma has long known how to conduct large post-marketing studies. But the associated cost structure is not conducive to long-term follow-up research to answer lingering questions about a drug’s safety profile. With an overall, industry-wide squeeze on research dollars—coupled with increasing regulatory commitments to provide ongoing safety data—pharma needs to embrace a new way of thinking about post-marketing research.
New Models
One element of the present post-marketing study model that needs re-examining is the traditional reliance on using doctors as the sole method of reaching and recruiting patients. As with early phase trials, the approach has been to recruit doctors with the hope that they will enroll patients. Operationally and statistically, this approach is both costly and inefficient. Capable physicians interested in clinical research are very difficult to recruit and even harder to retain. Industrywide, there’s a roughly 50 percent physician dropout rate over a one-year period. Short of paying doctors an enormous fee to make this type of research worth their time (and risking fraud and abuse allegations), most trial sponsors end up spending lots of money and end up very disappointed with the limited data they’ve collected 12 to 18 months down the line. This makes it very difficult to get the kind of data that we need, pushes back study timelines dramatically, and adds burdensome costs.
An alternative to this doctor-centric recruiting and reporting model is a system that includes a concept called patient-driven, doctor-reported data. Although not appropriate for trials in which rater consistency is essential, a system in which the patient can report his or her own outcome data back to the doctor can expedite a study and make the doctor’s participation far less taxing. Particularly with safety studies—in which the objective is just to confirm the presence or absence of a particular adverse event—the advantages of patient-driven, doctor-reported data can be substantial. And given the advances in technology that have enabled more widespread use of electronic patient reported outcomes, clinical trial data gathered in this manner is more timely and reliable.
The idea, essentially, is to register the patient upfront and provide the follow-up forms directly to the patient. Throughout the study, the patient can take the medical follow-up forms to a doctor—any doctor—and the doctor completes the form and submits the CRF. So the data is still doctor reported, but it’s the patient that’s driving the process. And instead of having a site-to-site trial structure, you’ve got a structure that is more patient-to-patient; which is entirely different than the traditional model.
Comfort with Change
Arguably the biggest hurdle in restructuring the current post-marketing trial structure is for industry to get comfortable with a whole new approach. This is really much more of an internal challenge than an external one. Moving forward with a new model for post-marketing studies also must involve the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMEA)—both must accept some elements of any new model as part of the negotiations around commitment studies. At the same time, however, pharma needs to pressure the regulators to come up with approval pathways. Regulators don’t just come up on the mountain and say, “This is our vision for the future.” Sometimes it would be nice if they did, but the point is to instigate an ongoing dialogue between all stakeholders and forge a partnership for change.
The objective of this partnership—as with any post-marketing study—is to increase the quality and timeliness of prospective surveillance data. And rather than just flogging the existing clinical trials methodology with more of a whip, or more money, we need to retool our processes and our approach on how best to obtain this data. For industry, having good safety data in hand enables companies to proactively show that their drugs are good for certain conditions, but may not be so for others. If companies are learning this early in the studies and are able to control the way that information is communicated to the public, they can stay in front of the PR curve. Further, they can effectively position that knowledge to win and maintain the public’s trust. Given the declining reputation of our industry, maintaining and restoring the public’s trust—by being transparent and proactive—is essential for the industry’s long-term sustainability.
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