Antipsychotic Trial Designs Still Not Reaching Scientific Standards

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Too many studies of atypical antipsychotic medications are still not meeting even the minimum scientific standards of the internationally agreed-upon CONSORT guidelines for drug trials, according to a study in Psychological Medicine. The frequently poor trial designs and methods are “potentially impeding the progress of research on antipsychotic efficacy,” stated the team from the Kings College London Institute of Psychiatry.

The researchers conducted a systematic analysis of all phase II and phase III clinical trials of antipsychotic drugs performed between 2006 and 2012. (ClinicalTrials.gov defines phase I trials as those involving testing a new drug in a small group for the first time, whereas phase II and III trials involve testing a drug in larger groups to see if is truly effective and to monitor side effects while comparing it to other commonly used treatments.)

The Kings College London researchers evaluated the antipsychotic trials on the basis of the scientific standards of their trial designs and reporting, assessing them relative to the international Consolidated Standards of Reporting Trials (CONSORT) guidlines. According to its website, CONSORT “offers a standard way for authors to prepare reports of trial findings, facilitating their complete and transparent reporting, and aiding their critical appraisal and interpretation.” Their guidelines have been endorsed by hundreds of medical journals.

The researchers evaluated 32 antipsychotic studies in total. “There was insufficient reporting of design in 47% of studies and only 13% explicitly stated a primary hypothesis,” the researchers found. “Exclusion criteria were poorly reported for diagnosis in 22% of studies. Detail regarding comparators, particularly placebos, was suboptimal for 56% of studies, and permitted concomitant medication was often not reported (19%). Randomization methods were poorly described in 56% of studies and reporting on blinding was insufficient in 84% of studies. Sample size calculations were insufficiently reported in 59% of studies.”

In conclusion, the researchers wrote that, “The quality of reporting of phase II and III trials for new antipsychotics does not reach the standards outlined in the CONSORT guidelines. Authors often fail to adequately report design and methodological processes, potentially impeding the progress of research on antipsychotic efficacy.”

(Abstract) The quality of reporting of phase II and III trials for new antipsychotics: a systematic review (Patel, M.X. et al. Psychological Medicine. February 2015. DOI: http://dx.doi.org/10.1017/S0033291714001214.)

Question: What are clinical trial phases? (ClinicalTrials.gov)

CONSORT website

5 COMMENTS

    • A little exercise in translation:
      “Exclusion criteria were poorly reported for diagnosis.”
      We picked the responders.

      “Detail regarding comparators, particularly placebos, was suboptimal for 56% of studies”
      Our drug didn’t do better than the placebo so we did our utmost to hide it.

      “Randomization methods were poorly described in 56% of studies”
      We picked the responders even more.

      “reporting on blinding was insufficient”
      We had to convince people that the drug was working (and they figured out they were on the pill anyway by the amount of side effects) and convince ourselves that we see “improvement” in the “right group”.

      “Sample size calculations were insufficiently reported in 59% of studies.”
      Well, we tested a small number of people many times and picked the studies which showed a positive effect. A bigger group would probably annihilate the effect so we didn’t bother to expand the trial.

  1. “potentially impeding the progress of research on antipsychotic efficacy,”

    Efficacy? What Efficacy?

    This is the VA.

    http://www.mirecc.va.gov/visn3/education.asp

    Algorithms:
    A review of existing algorithms, including VA National Guidelines, APA, the Texas Medication Algorithm Project (TMAP), and PORT was conducted. After careful consideration, a modified version of TMAP was selected, and named the New Jersey Algorithm.

    The sequence includes two trials of atypical antipsychotics followed by a Clozaril trial. If no favorable response is observed, a third atypical neuroleptic is tried, followed by a typical neuroleptic, followed by a combination of antipsychotic medications. The consensus of the internal advisory committee was to provide a flexible algorithm that will allow for minor modifications as new research is disseminated. Though a positive outcome has not been observed with the NJ Algorithm to date, researchers suspect that a larger sample size might generate significant findings in the future.

    “Though a positive outcome has not been observed ”

    This is the last summation of the size of the VA itself I have on hand.

    The Department of Veterans Affairs, through the Veterans
    Health Administration (VHA), operates a system
    comprising 153 medical centers, 882 ambulatory care
    and community-based outpatient clinics, 207 Vet Centers,
    136 nursing homes, 45 residential rehabilitation
    treatment programs, and 92 comprehensive home-based
    care programs—all providing medical and related services
    to eligible veterans. Those facilities provide inpatient
    hospital care, outpatient care, laboratory services, pharmaceutical
    dispensing, rehabilitation for a variety of disabilities and conditions,
    mental health counseling, and custodial care. VHA facilities employ
    about 200,000 fulltime-equivalent employees, including over
    13,000 physicians and nearly 55,000 nurses.

    All of that, and no positive outcome no matter which drugs they use, singly or in combination.

    “potentially impeding the progress of research on antipsychotic efficacy,”

    Notice the way it’s parsed.

    The VA isn’t addressing the actual efficacy of these drugs.

    They’re addressing the “progress of research” on them, or in plain English; How much longer can they continue to bamboozle the public into supporting their quest for funding “efficacy”.

  2. If the purpose of antipsychotics is to make a person psychotic, I for one can vouch for their efficacy. I was a healthy person with no personal or family history of mental health issues. I was put on a bad drug cocktail, including a “safe smoking cessation med” / antidepressant, by a PCP who wanted to cover up her husband’s “bad fix” on a broken bone of mine. The common ADRs and withdrawal effects of this antidepressant were misdiagnosed as “bipolar.” I was put on an antipsychotic, and within two weeks, I suffered a “psychotic” episode.

    The antipsychotics are effective at creating psychosis in healthy people.