Stefan Leucht1,2, Spyridon Siafis1, Rolf R Engel3, Johannes Schneider-Thoma1, Irene Bighelli1, Andrea Cipriani4,5, Toshi A Furukawa6, John M Davis7,8. 1. Department of Psychiatry and Psychotherapy, School of Medicine, Technical University of Munich, Munich, Germany. 2. Department of Psychosis Studies, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK. 3. Department of Psychiatry and Psychotherapy, School of Medicine, Ludwig-Maximilians-University of Munich, Munich, Germany. 4. Department of Psychiatry, University of Oxford, Oxford, UK. 5. Oxford Health NHS Foundation Trust, Warneford Hospital, Oxford, UK. 6. Department of Health Promotion and Human Behavior and Department of Clinical Epidemiology, Graduate School of Medicine/School of Public Health, Kyoto University, Kyoto, Japan. 7. Department of Psychiatry, University of Illinois at Chicago, Chicago, IL, USA. 8. Department of Psychiatry, Johns Hopkins School of Medicine, Baltimore, MD, USA.
Abstract
BACKGROUND: The magnitude of the superiority of antipsychotics over placebo is debated. One reason is that the effect-size index which is usually used in meta-analyses is in standard deviation units. Many other indices, some of which are more intuitive, exist. METHODS: We explain the formulae, advantages, and limitations of 13 effect-size indices: Mean Difference (MD), Standardized-Mean-Difference (SMD), Correlation Coefficient, Ratio-of-Means (RoM, endpoint and change data), Improvement Fraction (IF), Drug-Response Fraction (DRF), Minimally-Clinically-Important-Difference-Units (MCIDU), Number-Needed-to-Treat-derived from SMD (NNT), Odds Ratio (OR), Relative Risk (RR), and Risk Difference (RD) derived from SMD, Drug-response and Placebo-response in percent. We applied these indices to meta-analyses comparing antipsychotic drugs with placebo for acute schizophrenia. RESULTS: The difference of all antipsychotics pooled vs placebo (105 trials with 22741 participants) was: MD 9.4 (95% CI 8.4,10.2) PANSS points, SMD 0.47 (0.42,0.51), Correlation coefficient 0.23 (0.21,0.25), RoM endpoint 0.83 (0.81,0.85), RoM change 1.94 (1.84,2.02), IF (%) 49 (46,51), DRF (%) 94 (84,102), MCIDU 0.63 (0.56,0.68), NNT 5 (5,6), OR 2.34 (2.14, 2.52), RR 1.67 (1.59,1.73), RD 20% (18-22), and 50% (48, 52) improved on drug compared to 30% on placebo. Results of individual drugs compared to placebo are presented, as well. CONCLUSIONS: Taken together these indices show a substantial, but not a large superiority of antipsychotics compared to placebo. The general chronicity of the patients in the trials must be considered. Future meta-analyses should report other effect size indices in addition to the Standardized-Mean-Difference, in particular percentage responders in the drug and placebo groups. They can be easily derived and would enhance the interpretation of research findings.
BACKGROUND: The magnitude of the superiority of antipsychotics over placebo is debated. One reason is that the effect-size index which is usually used in meta-analyses is in standard deviation units. Many other indices, some of which are more intuitive, exist. METHODS: We explain the formulae, advantages, and limitations of 13 effect-size indices: Mean Difference (MD), Standardized-Mean-Difference (SMD), Correlation Coefficient, Ratio-of-Means (RoM, endpoint and change data), Improvement Fraction (IF), Drug-Response Fraction (DRF), Minimally-Clinically-Important-Difference-Units (MCIDU), Number-Needed-to-Treat-derived from SMD (NNT), Odds Ratio (OR), Relative Risk (RR), and Risk Difference (RD) derived from SMD, Drug-response and Placebo-response in percent. We applied these indices to meta-analyses comparing antipsychotic drugs with placebo for acute schizophrenia. RESULTS: The difference of all antipsychotics pooled vs placebo (105 trials with 22741 participants) was: MD 9.4 (95% CI 8.4,10.2) PANSS points, SMD 0.47 (0.42,0.51), Correlation coefficient 0.23 (0.21,0.25), RoM endpoint 0.83 (0.81,0.85), RoM change 1.94 (1.84,2.02), IF (%) 49 (46,51), DRF (%) 94 (84,102), MCIDU 0.63 (0.56,0.68), NNT 5 (5,6), OR 2.34 (2.14, 2.52), RR 1.67 (1.59,1.73), RD 20% (18-22), and 50% (48, 52) improved on drug compared to 30% on placebo. Results of individual drugs compared to placebo are presented, as well. CONCLUSIONS: Taken together these indices show a substantial, but not a large superiority of antipsychotics compared to placebo. The general chronicity of the patients in the trials must be considered. Future meta-analyses should report other effect size indices in addition to the Standardized-Mean-Difference, in particular percentage responders in the drug and placebo groups. They can be easily derived and would enhance the interpretation of research findings.
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Authors: Yikang Zhu; Chunbo Li; Maximilian Huhn; Philipp Rothe; Marc Krause; Irene Bighelli; Johannes Schneider-Thoma; Stefan Leucht Journal: Eur Neuropsychopharmacol Date: 2017-06-29 Impact factor: 4.600
Authors: Stefan Leucht; Johannes Hamann; Spyridon Siafis; Nicola Bursch; Katharina Müller; Lisa Schmid; Florian Schuster; Jakob Waibel; Tri Huynh; Florian Matthes; Alessandro Rodolico; Peter Brieger; Markus Bühner; Stephan Heres Journal: BMC Psychiatry Date: 2022-06-17 Impact factor: 4.144