by Christopher Jerome, PhD
Associate Vice President of Industry Research Collaboration
Pharmaceutical, biotechnology and medical device companies can spend millions of dollars on research and development just to get potential new treatments to the preclinical development stage. Even at that point, R&D teams are just starting to assess whether the new therapy or device has the potential to be safe and effective in humans.
After each preclinical study, companies face an important choice: Should the drug or device continue through the next stage-gate of development?
The go/no-go decision has major financial implications. Positive preclinical results that lead to positive clinical trials and eventually FDA approval can turn those R&D efforts into a new revenue stream for the company — and lead to better outcomes for patients.
Products that do well in preclinical trials but aren’t successful in human trials, however, represent a significant cost for any medical device or pharmaceutical company. And, as medical drug and device makers know, the odds are not favorable. Just one-third of therapies showing efficacy in preclinical studies result in clinical trials with statistically significant, positive results on the condition being studied.
The number of clinical trials that result in marketable therapies is even lower. Only 11 percent of drug therapies evaluated in human trials ultimately gain FDA approval.
While it’s impossible to remove all the risk and uncertainty from drug and medical device development, companies can make smarter decisions about whether to move ahead at each stage-gate of development.
Preclinical Roles for Clinician-Scientists
Expert clinicians, particularly MD-PhDs who work in an academic medical center and have collaborative relationships with other scientists, can have three positive impacts on preclinical research.
These clinician-scientists can:
- Help design preclinical trials that better simulate clinical applications.
- Anticipate problems that might otherwise not surface until the clinical stage of development.
- Assess the “user friendliness” of a potential product, suggesting ways to make the device or therapeutic more effective in clinical settings.
Characteristics of Effective Clinician-Scientists
Clinicians can be a boon to preclinical research. Clinicians who bring the most to preclinical research have several common characteristics.
An understanding of preclinical research. These doctors understand the challenges of basic research, making them better collaborators with their basic science counterparts. MD-PhDs, for example, or physicians who have done translational research, may be better prepared for the differences between preclinical and clinical trials.
Access to a multi-disciplinary team of collaborators. Though clinical input is undoubtedly helpful, clinicians with access to multi-disciplinary collaborators bring more to preclinical trials. Those collaborators — clinicians in other specialties, statisticians, scientists and project managers — can improve and even speed up the design, conduct and analysis of preclinical trials.
Access to high-quality lab equipment, animal care facilities and technical capabilities. Clinicians who have the resources and capability of conducting studies within their own institution will be better able to devote their full expertise to the study than if they simply consult on a remote study.
Designing better preclinical trials. Preclinical studies are a well-established way of testing whether a device or therapy is safe and likely to be efficacious in humans. However, the low rate of therapies ultimately approved for human use suggests better preclinical trials are needed.
Clinicians can suggest experimental procedures that more closely simulate a likely human application of a potential product. They can apply their deep knowledge of human biology and disease states, as well as patient behavior, to preclinical trials. They can develop the experimental design to be as close as possible to the likely clinical experience. This can lead to truer outcomes that provide better translational data for companies’ product developers, who will have to red-light or green-light a product for further trials once the preclinical study is complete.
Anticipating problems. Preclinical trials involving nonhuman subjects are, by definition, different from the clinical studies that may follow. Clinicians can anticipate problems that could arise during eventual clinical trials.
Because clinicians receive human patient feedback about diseases and treatments in their clinics, they can offer a critical understanding of how therapeutics and devices affect humans that is hard to ascertain from animal subjects. This understanding is especially significant in fields such as neuroscience, in which the therapeutic target is behavior, not just physiology. Clinicians can also spot potential landmines that could lie between preclinical and clinical trials. This allows researchers to design better studies, both at the preclinical and clinical stages. It also allows companies to more accurately assess the true clinical and commercial potential of a prospective new therapy.
Assessing user friendliness. Clinicians are best equipped to assess the user friendliness of a therapy or medical device. In the case of many medical devices, clinicians are the intended end users of the device.
No matter how smart the engineering behind a new device, if it’s difficult to use, it’s not likely to be well received in the marketplace. Imagine a medical device intended for implantation in a patient’s body. Even if it’s easy to implant in a nonhuman subject, a surgeon involved in a preclinical trial will likely anticipate whether implantation in a human patient will be just as easy — or not. That insight during the preclinical stage can reduce re-engineering later in the development process, when it will be costlier.
The bottom line: Next time you’re planning a preclinical study, consider how including a clinician on the research team might improve your study results.
Visit WakePreclinical.com to learn more about Wake Forest Baptist Medical Center’s preclinical research solutions for industry.
About the Author
Christopher Jerome, PhD, leads the Center for Industry Research Collaboration at Wake Forest Innovations. The Center works with industry to expedite access to specialized clinical and research capabilities of Wake Forest Baptist Medical Center. Contact him at firstname.lastname@example.org.