In June 2017, Yale CRIT hosted an international conference titled “Ensuring Safety, Efficacy, and Access to Medical Products in the Age of Global Deregulation.” The following blogpost is the eighth installment of a blog series with commentaries from the conference participants. The views and opinions expressed in this blogpost are those of the author and do not necessarily reflect the position of Yale CRIT. For more blogposts related to this series, see here or click the tag “YaleCRIT17” below.
How can we support evidence-informed practice if the vast majority of the research on drugs is flawed?
Clinical studies supporting market authorizations of new drugs are all designed, conducted, and reported by the companies that will market them. Often these trials have deficiencies in their design, such as enrolling too few participants to be conclusive or measuring outcomes that are not good predictors of clinical benefit.
On top of these concerns, the current shift toward early regulatory approvals seems to go in an even worse direction for clinical research. For instance, the so-called adaptive pathways piloted in Europe are intended to overcome the dichotomy “pre- and post-market” and implement an iterative development, with approval in stages. Under the “adaptive” regime, approvals can be granted for a restricted group of patients and then expanded to wider populations, or may be based on surrogate endpoints considered—but not necessarily proved—predictive of important clinical outcomes.
Despite these shortcomings and concerns, alternative scenarios in which clinical evidence counts less in regulatory and medical decision-making is frightening. The risk with abdicating evidence-informed practice altogether is tossing the baby out with the bathwater.
The state of clinical research is far from optimal, and we must keep working to improve it.
First, the pharmaceutical environment is problematic, but it is also highly regulated. Therefore, public policies and regulatory agencies can drive quality and value in clinical research, for example through guidelines and early development scientific advice. Regulators, if they really aim to serve no other interests but public health, have the responsibility to keep the standards high. They should require evidence of clinical benefit over available alternatives at the time of approval and not just the demonstration that drugs are of good quality, intrinsically safe and efficacious. They should rely on early approval only as exceptions, develop agreed and detailed definitions of when they are applicable, and ensure that post-marketing evidence is accurate, timely, reliable, and transparent to fill the gaps left by pre-market evidence. In other words, they should not be tempted by hope (or hype)-based medicine.
Second, clinical researchers can be taught to recognize and avoid bad research practices. Researchers are doctors and other health professionals often working in public hospitals and universities. Some of them have conflicts, but others simply do not have enough training to understand they are the armed branched of biased research. Moreover, their career development needs and their institutions’ ambitions prompt them to enrol patients into flawed, irrelevant, or even potentially harmful trial protocols. We should allow good doctors and health professionals to be engaged in research projects which have patients’ and health services’ needs at the core. They will learn and—one hopes—be convinced that doing relevant and well-designed trials is possible and gratifying.
Finally, non-commercial research should have a role in shaping the knowledge about the drugs we use and pay for. Public research is poorly represented in the current drug development model, where evidence supporting drug approvals is generated by commercial trials. The needs of health services and practitioners should be translated into research questions for pragmatic comparative effectiveness trials and active pharmacovigilance studies. Proper funding is necessary but not sufficient: only with the alignment between public research investments and healthcare priorities will public research play a pivotal role.
Rita Banzi, Ph.D. is a specialist in Clinical Pharmacology at Laboratory of Drug Regulatory Policies, Mario Negri Institute for Pharmacological Research in Milan, Italy.