For Roger J. Porter, MD, March kicked off his two-year term as the president of the American Society for Experimental NeuroTherapeutics (ASENT), a nonprofit, scientific organization of 300 representatives from academia, government, advocacy groups, and industry focused on developing improved therapies for neurological disorders. Dr. Porter considers himself a hybrid of all four groups, having moved among them throughout his career.
A neurologist, he spent 20 years at the NINDS, mostly in clinical epilepsy research, and held positions as chief of the Epilepsy Branch, chief of the Medical Neurology Branch, and deputy director of the NINDS. In 1992 he left the NIH to become vice president for clinical pharmacology at Wyeth-Ayerst Research, rising to deputy head of clinical research for all of Wyeth Pharmaceuticals by the time he retired in 2003.
Currently, in addition to his leadership at ASENT, he serves as a private consultant for the pharmaceutical industry, chiefly in the development of antiepileptic drugs, and as adjunct professor of neurology at the University of Pennsylvania and adjunct professor of pharmacology at the Uniformed Services University of the Health Sciences. His publications include 13 books and 299 papers and abstracts.
Dr. Porter spoke with Neurology Today about how far the organization — which evolved from the AAN Committee on Neuropharmacology — has come since he was a founding member of ASENT in 1997.
WHAT ARE SOME OF ASENT'S PRIORITY ISSUES?
The number one priority is to provide a communication forum for neurotherapeutics that brings together colleagues from academia, advocacy, industry, and government, as equals. Our annual meeting is always held in the Washington, DC, area in March. We focus on major issues in clinical neuroscience, clinical trial methods, public policy, ethics, and social issues. Our program focuses more on clinical science, but I think we will also continue to have basic science forums in the future.
We also educate our members as well as residents and fellows in neuroscience on the science of clinical trials. We do this through our peer-reviewed journal, Neurotherapeutics, edited by Dr. Alan Faden and published quarterly. Also, we have a daylong course at our annual meeting in March that focuses on clinical trials.
The real ongoing benefit of membership in ASENT is the collaborative interactions that are often initiated at the annual meeting or fostered during the rest of the year. We would like to see the membership grow to 400–500 over the next few years.
TELL US MORE ABOUT ASENT'S FOCUS ON GLOBALIZATION AND THE DEVELOPMENT AND AVAILABILITY OF TREATMENTS FOR NEUROLOGICAL DISORDERS?
Globalization refers to harmonizing regulatory practices, getting small companies to present new ideas to large, global companies, and exposing exciting ideas from academia to both large and small companies — all to promote the development of new therapies.
The immediate past-president, Dr. Alan Faden, is working to begin an international umbrella organization to encourage similar national organizations to form. There is already a society in Germany, GSENT, which shares our mission, and a similar society in Japan. Dr. Faden has planned an organizational meeting in Europe, which should take place as soon as funding is secured.
HOW DO ADVOCACY GROUPS WORK WITH ASENT TO PROMOTE TRANSLATIONAL RESEARCH?
Although one critical step is to take a therapy into a clinical trial, it is often risky; advocacy teams are now rethinking how to use their limited resources to get the most advantage for their particular disorder. Examples include all the drugs that have been tried in clinical trials for stroke, from which very few important therapies (aside from tPA) have emerged. At the ASENT annual meeting, there is always a session that focuses on advocacy issues and the collaboration between academia, advocacy, government, and industry. One challenge for us is to sustain this ongoing collaboration throughout the year.
WHAT ARE THE CHALLENGES OF CONDUCTING TRANSLATIONAL RESEARCH?
The new interest in translational research is reflected in the NIH funding push for translational medicine. This has affected clinical research units funded by the NIH, and has, to some extent, enhanced the status of clinical research. We are still in need of developing academic clinical investigators who focus on identifying interventions to improve health care. ASENT wants to bring more academic investigators to the bedside. ASENT is the ideal forum for translational neuroscience — moving our knowledge from academia to industry, or from the mouse to the patient.
IS LIABILITY RISK IN TRIALS HURTING THE NUMBERS OF TRIAL ENROLLMENT?
While safety problems do sometimes occur, remarkably few patients are injured in clinical trials. Also, liability issues are not significant for trial enrollment.
What really hurts clinical trial enrollment is that many potential subjects are unaware of the availability of the trials. In general, only a small percentage of available subjects are being enrolled. One reason is an overall decrease in interest in clinical trials in both patients and physicians. Another challenge to enrollment occurs if a patient has not fully exhausted the available marketed therapies, in which case the potential referring doctor may not recommend a clinical trial. We need a better means of communicating trial availability to patients. The new Web-based trial listings help, but more needs to be done and there are no quick fixes.
WHAT ABOUT LEGISLATION TO PROMOTE MORE INFORMATION ABOUT ADVERSE EFFECTS?
In October of 2007 the US Congress passed the FDA Amendments Act of 2007, which included the requirement that nearly all clinical trials in the US must be registered on ClinicalTrials.gov, a Web site operated by the National Library of Medicine. It is currently in effect. In addition, Congress required that the results of the studies should be posted, and this requirement will go in effect later this year.
WHAT AREAS NEED MORE HELP IN TERMS OF TRANSLATIONAL RESEARCH?
For many years, pharmaceutical industry research and development funding as a percent of revenues has been at the highest level of any major industry. If these revenues decline, the funds available for future research and development will also decline. Further, the scientific search for new drugs and devices has become more challenging, because we are tackling the more difficult problem of treating diseases at their basic causes rather than developing symptomatic treatments. At least for large pharmaceutical companies, keeping research monies stable in this new environment will be difficult.
CAN RESEARCHERS WHO DEPEND ON INDUSTRY SUPPORT BE FREE OF CONFLICTS OF INTEREST?
Contrary to popular opinion, controlled clinical trials conducted by the industry (especially large pharmaceutical companies) are designed to be as bias-free as possible. Many protocols are pre-approved by the FDA and a large number are conducted at academic centers. In most pivotal trials, a number of controls are placed on each trial to assure objectivity, such as randomization, double blinding, and intense monitoring of trials by trained experts. Most important trials also include a large number of independent centers to limit bias. Because a trial may be submitted to the government for drug registration and marketing, each company knows that the regulatory agencies will be scrutinizing the trial for any kind of bias or fraud. Since these trials typically cost millions of dollars each, the industry wants the trial to be “clean.”
Problems of conflict of interest still remain, however, including such issues as pre-publication review and potential withholding of data. The impact of these events has been minimal relative to the total number of trials conducted, but concerns about such issues are part of ASENT's mission. And because industry is dependent on qualified academic investigators for clinical trials, the partnership between academia and industry must continue to ensure that drug development proceeds at a reasonable pace.
To learn more about ASENT, visit http://www.asent.org.