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Schizophrenia trails - past, present, future Mahesh Jayaram.

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Presentation on theme: "Schizophrenia trails - past, present, future Mahesh Jayaram."— Presentation transcript:

1 Schizophrenia trails - past, present, future Mahesh Jayaram

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7 Schizophrenia trials....the past

8 Number of reports per year* * Thornley & Adams. BMJ, 1998

9 Number of reports per year* * Updated Jayaram 2007

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11 Source of trials (past) North America 54% Europe 37% South & Central America 1% Africa-Asia 5% Australia 2% Source of trials* * Thornley & Adams. BMJ, 1998

12 Source of trials (New Slide) Source of trials* * Updated Jayaram 2007 Unclear 8.5% South America 1% Multinational 1% Australia & NZ 2% Europe 29% North America 36% China 16% Rest of Asia 7% Africa 0.5%

13 Average size of trial over time* R 2 = Number of trials * Thornley & Adams. BMJ, 1998

14 * Updated Jayaram 2007 Average size of trial over time*

15 Frequency of trial size Number of studies Number of participants

16 Numbers of trials by duration 115 (6%) 9 (5%) 89 (4%) 169 (8%) 538 (27%) 801 (40%) 279 (14%) < 1 week 1-6 week >6wk-6mo >6mo-1yr >1yr-5yr 5+ yr Unknown Number of trials

17 Loss to follow-up 0% 10% 20% 30% 40% 50% 60% Clozapine Risperidone Olanzapine Quetiapine

18 Trials present - does systematically reviewing current and past studies help? Schizophrenia trials....the present

19 Two types of reviews

20 Traditional Systematic

21 Two types of reviews Traditional Systematic Winter, Don River

22 Winter, Don River; AJ Casson Two types of reviews Traditional Systematic Winter, Don River

23 Treatment BetterTreatment Worse Date RCT No p<.01 p<.001 p< * 6k 22k 47k 1 R / SpExpNm Textbook/Review recommendations From Antman et al, 1992 Thrombolytic therapy for acute MI

24 Increasing impact of systematic reviews

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27 Jayaram, Hosalli & Stroup

28 Schizophrenia trials....future

29 Explanatory vs pragmatic trials Participants - rigorously diagnosed vs clinical diagnosis Interventions - rigid regimens vs clinical judgement Outcomes - meticulously measured outcomes vs outcomes that you would be embarrassed not to record in the notes

30 CUtLASS and CATIE

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32 $$$$$$$ $$$$$$$ $$$$$$$ $$$$$$$ $$$ ££

33 Olanzapine vs amisulpride - before 1 42/188 39/ (0.74, 1.59) vs amisulpride - after 2 55/245 42/ (0.74, 1.54) Sulpiride vs Amisulpride 1 27/58 3/ (0.72, 5.65) vs Olanzapine 1 27/58 13/ (1.04, 3.08) vs Perphenazine 2 10/55 16/ (0.24, 1.87) vs Quetiapine 1 27/58 12/ (0.55, 1.44) Risperidone vs Olanzapine - before 9 228/ / (1.14, 1.55) vs Olanzapine - after / / (1.10, 1.28) vs Quetiapine - before 1 59/ / (0.83, 1.35) vs Quetiapine - after 3 321/ / (0.84, 1.00) vs Perphenazine - before 1 4/55 15/ (0.47, 1.64) vs Perphenazine - after 2 267/ / (0.90, 1.08) vs Amisulpride - before 1 32/113 37/ (0.59, 1.31) vs Amisulpride - after 2 41/135 40/ (0.58, 1.80) vs Sulpiride 1 27/58 9/ (0.64, 2.02) RCTs n/N n/N RR (random) CI (95%) Outcome: Leaving the study early – before and after Leaving the study early

34 Forrest Plot

35 Study IDs

36 Forrest Plot Sample sizes

37 Forrest Plot Line of no difference

38 Forrest Plot Line of no difference Pooled result

39 Olanzapine vs amisulpride - before 1 42/188 39/ (0.74, 1.59) vs amisulpride - after 2 55/245 42/ (0.74, 1.54) Sulpiride vs Amisulpride 1 27/58 3/ (0.72, 5.65) vs Olanzapine 1 27/58 13/ (1.04, 3.08) vs Perphenazine 2 10/55 16/ (0.24, 1.87) vs Quetiapine 1 27/58 12/ (0.55, 1.44) Risperidone vs Olanzapine - before 9 228/ / (1.14, 1.55) vs Olanzapine - after / / (1.10, 1.28) vs Quetiapine - before 1 59/ / (0.83, 1.35) vs Quetiapine - after 3 321/ / (0.84, 1.00) vs Perphenazine - before 1 4/55 15/ (0.47, 1.64) vs Perphenazine - after 2 267/ / (0.90, 1.08) vs Amisulpride - before 1 32/113 37/ (0.59, 1.31) vs Amisulpride - after 2 41/135 40/ (0.58, 1.80) vs Sulpiride 1 27/58 9/ (0.64, 2.02) RCTs n/N n/N RR (random) CI (95%) Outcome: Leaving the study early – before and after Leaving the study early

40 Olanzapine vs amisulpride - before 1 42/188 39/ (0.74, 1.59) vs amisulpride - after 2 55/245 42/ (0.74, 1.54) Sulpiride vs Amisulpride 1 27/58 3/ (0.72, 5.65) vs Olanzapine 1 27/58 13/ (1.04, 3.08) vs Perphenazine 2 10/55 16/ (0.24, 1.87) vs Quetiapine 1 27/58 12/ (0.55, 1.44) Risperidone vs Olanzapine - before 9 228/ / (1.14, 1.55) vs Olanzapine - after / / (1.10, 1.28) vs Quetiapine - before 1 59/ / (0.83, 1.35) vs Quetiapine - after 3 321/ / (0.84, 1.00) vs Perphenazine - before 1 4/55 15/ (0.47, 1.64) vs Perphenazine - after 2 267/ / (0.90, 1.08) vs Amisulpride - before 1 32/113 37/ (0.59, 1.31) vs Amisulpride - after 2 41/135 40/ (0.58, 1.80) vs Sulpiride 1 27/58 9/ (0.64, 2.02) RCTs n/N n/N RR (random) CI (95%) Outcome: Leaving the study early – before and after Leaving the study early Jayaram, 2007, in press

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47 I-IV TREC-Rio-1 (n=300) TREC-India-1 (n=200) TREC-Rio-2 (n=316) TREC-India-2 (n=300)

48 I-IV TREC-Rio-1 (n=300) TREC-India-1 (n=200) TREC-Rio-2 (n=316) TREC-India-2 (n=300) The UK PROMPTS (n=764)

49 I-IV TREC-Rio-1 (n=300) TREC-India-1 (n=200) TREC-Rio-2 (n=316) TREC-India-2 (n=300) LEEDS - Leeds Evaluation of Efficacy of Detoxification Study – Homeless (n=60) – HMP Armley(n=90) – Multi-prison(n=340) The UK PROMPTS (n=764)


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