Are Adaptive Trials Ready For Primetime?
It is well-known that many patients volunteer for clinical trials because they mistakenly believe that the goal of the trial is to improve outcomes for the volunteers. A type of trial that does attempt to improve outcomes for those who enter into the trial late is the adaptive trial. In adaptive trials investigators change the enrollment and treatment procedures as the study gathers data from the trial about treatment efficacy. For example, if a study compares a new drug against a placebo treatment and the drug appears to be working, subjects enrolling later will be more likely to receive it. The idea is that adaptive designs will attract more study volunteers.
As pointed out in a couple of recent commentaries, however, there are many unanswered questions about this type of trial. A major concern is the problem of unblinding that may occur with this design with resulting problems with allocation of patients to groups. Frequent peeks at the data may influence decisions made by monitoring boards, investigators and participants. Another issue is the unknown ability to replicate adaptive trials. Finally, there are ethical questions such as the issue of greater risk for early enrollees compared to risk for later enrollees.
For further information see—
1. Adaptive Trials in Clinical Research: Scientific and Ethical Issues to Consider
van der Graaf R, Roes KC, van Delden JJ. Adaptive Trials in Clinical Research: Scientific and Ethical Issues to ConsiderAdaptive Trials in Clinical Research. JAMA. 2012 Jun 13;307(22):2379-80. PubMed PMID: 22692169.
2. Adaptive Clinical Trials: A Partial Remedy for the Therapeutic Misconception?
Meurer WJ, Lewis RJ, Berry DA. Adaptive clinical trials: a partial remedy for the therapeutic Misconception?adaptive clinical trials. JAMA. 2012 Jun 13;307(22):2377-8. PubMed PMID: 22692168.
Why People Tend to Overuse Healthcare Interventions
This nice piece in Time Magazine by Maia Szalavitz provides some clues about our major problem of overuse. Ms. Szalavitz documents the convincing power of anecdotes compared to statistics which are poorly understood by most people. She provides a really nice example of decision support from the Harding Center for Risk Literacy for prostate cancer screening that illustrates graphically how prostate cancer screening is likely to create more harms than benefits. For more information go to—
Critical Appraisal Matters
Most of us know that there is much variation in healthcare that is not explained by patient preference, differences in disease incidence or resource availability. We think that many of the healthcare quality problems with overuse, underuse, misuse, waste, patient harms and more stems from a broad lack of understanding by healthcare decision-makers about what constitutes solid clinical research.
We think it’s worth visiting (or revisiting) our webpage on “Why Critical Appraisal Matters.”
Safety Review of Five Biologic Antirheumatic Drugs
An abstract of ours was selected for publication by the The European League Against Rheumatism (EULAR) for their Annual European Congress of Rheumatism 2012. We believe that our review provides important safety information for providers and patients. While the evidence has to be considered borderline at best due to study design and methodology issues (much is observational, for example), we believe the patterns are highly compelling, consistent and that they are not likely to be explained by a systematic bias. Therefore, we feel quite confident in the direction of the outcomes. (The link below is sometimes slow to load or needs to be loaded a subsequent time to view—so if it “fails to load,” try again.)
Stuart ME, Strite SA, Gandra SA. Systematic Safety Review Of Five Biologic Antirheumatic Drugs. Abstract number AB0478; EULAR 2012 Annual European Conference of Rheumatology
Dr. John Ioannidis on Clinical Trials Issues, Cost and Inappropriate Care
Since 1949, the NIH has provided a biweekly newsletter for employees of the National Institute of Health. Mostly the NIH Record announces talks to be given on-campus, but also summarizes some of the talks. In a recent issue the Record summarized a recent talk on bias in healthcare trials, delivered by Dr.John Ioannidis, director of the Stanford Prevention Research Center. Some of his key points are quite thought-provoking and relate to our our huge problem of costly and inappropriate care. Here is some food for thought from Dr Ioannidis:
- Most statistically significant findings are not real at all—they’re just false positives
- Many of these false positives are revealed when larger-scale studies attempt to replicate the findings of smaller studies
- One of every four such trials is refuted when a larger trial is conducted
- Journal editorial policies are responsible for much of this trend— editors want to see research that is novel and will have a large impact on the field. This generally means that editors are looking for papers that report very large, statistically significant effects.
- An important safeguard is “repeatability” of positive findings
- Individuals with a track record for doing high quality research should be recognized and given priority in publishing.
To read the entire entry go to: