Three Questions: Kashinah Yadalam, Lake Charles Clinical Trials
Monday, August 3, 2015
CWWeekly presents this occasional feature as a way to put the spotlight on issues faced by executives in the clinical trials space. Staff Writer Ronald Rosenberg sat down with Kashinah Yadalam, M.D., medical director and chief executive officer of Lake Charles Clinical Trials in Louisiana.
Q: A common theme in mental health is there are too many trials chasing too few patients. How has patient recruitment for schizophrenia and bipolar disorders changed in the last five years?
A: The volume of trials comes in waves. There are times when many trials are offered and then few to none. I understand that this may be due to the funding availability and the economy. Recently, due to a series of negative trials, there seems to be a hesitation among large pharmaceutical companies (Eli Lilly, Pfizer, BMS, etc.) to invest in CNS trials. Instead, we are seeing many smaller companies entering the arena. There are many unmet treatment needs of suffering patients—so sooner or later, I believe, the void will be filled.
Several years ago, there were so many requests to conduct trials that I would routinely refuse to accept two to three trials each month either because we were conducting similar trials or because our resources were fully spoken for. During the first two quarters of last year, the trials were few, and then slowly the new offers to conduct trials increased steadily. Clearly, when you have too many studies in the same disease state, recruiting is difficult, as one cannot manufacture these patients.
For us, conducting trials in acute schizophrenia—which generally involves inpatient hospitalization—is easier because we are affiliated with a large community hospital and there isn’t a dearth of patients that get admitted there that fit the criteria.
Bipolar mania is a different story. It is hard to enroll truly manic patients in trials because they are by nature very fickle and lose interest very quickly. Generally, sponsors conduct fewer bipolar mania trials because if the compound is approved to treat psychotic symptoms of schizophrenia, most practitioners prescribe it to treat acute manic symptoms as well. So, if the drug is safe and effective, it helps the sponsors and the patients.
Q: How have depression protocols changed in terms of complexity, time to enroll patients and time to complete studies?
A: The complexity and the number of assessments required has increased across the board, more so in schizophrenia trials, where screening visits can take up to six hours. In a way, this is unbelievable, but that’s the nature of the beast.
Sponsors tell us that regulators require these assessments for approval, but this needs to be carefully reconsidered by all the parties involved. Needless to say, at least in the case of major depression trials, the longer patients are at the clinical trials site, the more contact they have with treating personnel and this, in turn, has demonstrated a higher placebo response. That’s because patients are in an environment— institutional transference—that they perceive to be therapeutic.
It is unwise to put pressure on sites to enroll patients because that may result in poor data quality. Generally, before a trial starts, we are asked to estimate the number of subjects we can enroll and the quantity provided is based on our previous trial experience. Now, this can change due to a variety of reasons. When the indication is new or if the compound is radically different, there is more interest in the public and referral sources.
Lately, due to the publication of many negative trials in the lay media, particularly in Alzheimer’s disease, we have noted a reduction in patient interest in trial participation. In the past, clinical trials in depression enrolled subjects who may be suffering their first episode—which was not hard to enroll— but nowadays, protocols are designed for treatment-resistant depression. That’s where somebody must have failed once or twice— even three times—to be included in the trial, which makes it harder to enroll.
Q: Recent research shows clinical trials that address cognitive deficits in bipolar disorders face distinctive challenges. What are some of the major ones?
A: Cognitive testing in patients who are truly manic is a tall order by the very nature of the disease. As a rule, any cognitive testing that requires more than 45 minutes of sustained attention in an acutely ill population results in poor data quality.
Subjects who are in a depressed or in a remitted state of bipolar disorder will have less difficulty in cognitive assessment. Overall, keep the duration of cognitive assessment short for the better patient and rate acceptance—both can get fatigued—so the results will be more meaningful.
Email comments to Ronald at firstname.lastname@example.org. Follow @RonRCW
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