The Necessity of Randomized Clinical Trials.

Aims: The hierarchy of evidence-based medicine determines the inferential powers of different clinical research designs. We want to address the difficult question if observational evidence under some circumstances can validate intervention effects. Methodology: Assessment of previous argumentation aiming at a clear conclusion for future decision-making. Results: We present five arguments demonstrating the fundamental need of randomized clinical trials to sufficiently validate intervention effects. Furthermore, we argue that hindrances to the conduct of randomized clinical trials can be lessened through education, collaboration, infrastructure, and other measures. Our arguments validate why the randomized clinical trial should and must be the study design evaluating interventions. By choosing the randomized clinical trial as the primary study design, effective preventive, prognostic, diagnostic, and therapeutic interventions will reach more patients earlier. Conclusion: Clinical experience or observational studies should never be used as the sole basis for assessment of intervention effects — randomized clinical trials are always needed. Therefore, always randomize the first patient as Thomas C Chalmers suggested in 1977. Observational studies should primarily be used for quality control after treatments are included in clinical practice.

Is the Total Score of the Hamilton Depression Rating Scale Associated with Suicide Attempts or Suicides.

Background: Most evidence behind interventions for depression is, in essence, based on the total score of the 17-item Hamilton Depression Rating Scale (HDRS). We identified no systematic review or meta-analysis examining if a total 17-item HDRS score is associated with suicide attempts or suicides in depressive patients. Methodology: Based on a systematic literature search CENTRAL in The Cochrane Library, MEDLINE, EMBASE, PsycInfo, and Science Citation Index Expanded, we systematically reviewed and meta-analysed observational studies examining if the total 17-item HDRS score is associated with suicide attempts or suicides. Results: We identified and included ten cohort studies - seven retrospective and three prospective. All the studies were assessed as high risk of bias. Meta-analysis on the HDRS scores from three retrospective studies showed that depressive patients with a suicide attempt during the on-going depressive episode had a significantly higher score on the HDRS compared to non-suicidal patients (mean difference 6.31 HDRS; 95% confidence interval 4.72 to 7.91; P<0.00001, I2=0). However, meta-analyses of the HDRS scores from three prospective studies and four studies reporting retrospectively lifetime suicide attempts showed no significant differences between patients with or without a suicide attempt or suicide. Conclusion: A total score on the HDRS does not seem to be associated with past or future suicide attempts or suicides. There seems to be a need for other assessment tools to predict and explain risks of suicidality.