Schizophrenia has no cure. Current treatments only aim to contain the psychotic and social symptoms of the disorder. However, to get the most out of the clinical trials for schizophrenia relapse prevention medication, the government has allowed placebo controlled trials.
In a recent analysis, Professor Robin Emsley of the University of Stellenbosch and co-authors argue that such placebo trials are potentially putting the patients in harm’s way and that non-inferiority trials offer a suitable alternative.
The paper, published on 9th September, reached the conclusion that although contemporary research may be insufficient to define clear cut hazards of such trials, perils not yet known are likely to exist. The authors wrote: “No evidence of harm is different from evidence of no harm, and the burden must be to show no harm.” The paper called for long-term studies, designed to determine the mental and biological impacts the alarming placebo trials have on schizophrenic individuals and the relapse.
Circulating their analysis in the journal BMJ, the authors went on to cumulate and analyze the findings of recent paper on the matter and then presented the above mentioned verdict.
The latest research findings that were used as basis for their arguments were as follows: the damaging impacts resulting from a relapse need to continue the medication indefinitely and the new heightened ethical standards imposed on such trials.
Placebo clinical trials in general are considered controversial as the patient may be exposed to risk by discontinuation of an already proven therapy. Moreover, placebo dependent clinical trials are still more contentious for relapse prevention medication in schizophrenia because a long-term based evidence is required. As a result, the likelihood of suffering a relapse is significantly more, for the lengthy time period.
It should be noted here that this is not the first paper that has signified the shortfalls of placebo clinical trials for schizophrenia treatment. In a review paper published in 2013, two of the authors of the recent BMJ paper, Robin Emsley and Wolfgang W Fleischhacker, questioned whether the randomized placebo clinical trials for schizophrenia were transgressing ethical boundaries and concluded with an affirmative.
In the 2013 review the authors were assessing the effects of placebo in clinical trial studies of specifically antipsychotics for schizophrenics. The authors mentioned that the chance of a relapse shoots to an enormous 56% for enrolled schizophrenic patients in the placebo group. While those on actual treatment were at a significantly less risk of a relapse, at 17.4 %.
Clinical trials for schizophrenia fall in the grey zone of the ethical field, if looked through at by the World Medical Association’s Declaration of Helsinki. In particular, the practice appears to negate their guided principle number 8, which states that “While the primary purpose of medical research is to generate new knowledge, this goal can never take precedence over the rights and interests of individual research subjects”.
The current article lists three main excuses for why such placebo studies are conducted. The first is the apparent lack of evidence that placebo trials increase morbidity; the second that we can detect a possible relapse before it occurs and stop the placebo if needed; and lastly, an estimate that less overall relapses are needed to prove the medication in placebo controlled rather than in a comparison trial involving another medication.
In their recent article, the authors discuss that at several occasions, the clinical trials may prolong the placebo duration so as to record a psychosis event among the participants. This way the medication under trial may be portrayed for its protective outcome. The paper highlights that apart from the ethical, two scientific concerns also arise when conducting placebo trials for schizophrenia relapse prevention therapies.
The first concern is that there may already be a bias towards the treatment among individual who participate and their physicians. The writers put forth the argument that individuals who had little trust on the therapy in the first place are more likely to participate in the trials.
The study recalls the leading cause of people not wishing to participate as a fear of relapse: those who were convinced of the effectiveness of the therapy simply did not participate.
Hence, the sample population used in the trials is not an accurate depiction of all the schizophrenic individuals.
Another shortcoming of such trials, as reported by the BMJ study, is that patients often opt to drop out in the middle of the trial. This is usually out of a fear of a relapse.
But whatever the patient’s reason may be, the study loses its statistical significance once the number gets low enough.
By far, the most convincing arguments presented in Robin Emsley’s paper, which refutes the current defense of these placebo trials, is the statement that our current diagnosis of the signs and symptoms preceding a relapse is a lot more unreliable than such trials presume. When conducting, or participating in such trials, vigilance is the key.