BOCA RATON, FLA. – Clinicians treating alcohol abuse or depression could improve outcomes by adopting a strategy gaining popularity among psychiatry researchers, according to several presentations at a meeting of the New Clinical Drug Evaluation Unit sponsored by the National Institute of Mental Health.
With “adaptive design,” patients agree to begin a particular treatment with preset time points for gauging response or remission.
This “operationalization” of clinical trials has increased enrollment, improved patient engagement in their treatment, and allowed researchers to switch more patients to a better outcome by study end, Dr. David W. Oslin said.
A protocol that dictates initial treatment duration and when to switch patients to a different treatment removes some clinician judgment. This may make some physicians uncomfortable at first, said Dr. Oslin, Hazelden Research Co-Chair in late life addiction at the University of Pennsylvania, Philadelphia.
For example, Dr. Oslin and his associates are using adaptive design for a trial of naltrexone for alcohol abuse. “We chose 8 weeks. Patients had to make it to 8 weeks to be considered responders. This caused a considerable amount of angst.
The reason? Clinicians were not used to not making the decision of when to determine response,” according to Dr. Oslin.
“Alcoholism is the example, but you can substitute depression if you treat patients who are depressed,” Dr. Oslin said.
Adjusting treatment requires knowledge about when to change, how to define when (for a responder or nonresponder), and what to change to. “It's not trivial deciding when to give up on a particular agent,” Dr. Oslin said.
In the naltrexone study, about 40% of participants were drinking or not having a robust response in the middle of the trial. Changing their treatment resulted in about half of those in the poor outcome group switching to a good outcome by 8 weeks, Dr. Oslin said.
Responders in the naltrexone study are randomized to prescription plus telephone disease management and follow-up at 4 months, or prescription and follow-up at 4 months. Nonresponders receive combined behavioral intervention and medical management and are randomized to either naltrexone or placebo, Dr. Oslin said, “to essentially answer the question about benefits of continuing naltrexone.”
“If we adapt treatment at the point that people relapse, you retain more people and keep them longer in the program,” Dr. Oslin said.
“There may also be a spillover effect to the people who really did not engage at all or would have dropped out early.”
An unexpected finding was an increased willingness of patients to participate in the naltrexone study because of its design. Dr. Oslin said this finding makes sense.
“Most of us would be more willing to start in a program if we know treatment will be adapted depending on how we are doing, versus knowing someone is going to flip a coin and randomly assign us.”
“When we give a patient a medication or psychotherapy, we are doing an experiment. Often, we have to take a second step, third step, and fourth step,” said Dr. A. John Rush Jr., Rosewood Corporation Chair in biomedical science and Betty Jo Hay Distinguished Chair in mental health, University of Texas Southwestern Medical Center, Dallas.
With adaptive design, each treatment may inform the next step, Dr. Rush said at the meeting, which was cosponsored by the American Society for Clinical Psychopharmacology.
In addition, a treatment that appears best initially may not be the best in the long term, said Susan A. Murphy, Ph.D., who is H. Robbins Professor of statistics and senior research scientist at the Institute for Social Research at the University of Michigan, Ann Arbor.
Therefore, using adaptive design makes sense because it collects intermediate outcomes that can guide for whom each treatment works the best, Dr. Murphy added.