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Meta-analysis of dropout rates in randomized controlled clinical trials

Opioid analgesia for osteoarthritis pain

Metaanalyse zur Abbruchrate in randomisierten kontrollierten klinischen Studien

Opioidanalgesie bei Arthroseschmerz

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Abstract

Background

The interpretation of opioid studies in patients with chronic pain due to osteoarthritis is limited by a high dropout rate. Therefore, the implication of dropouts on the recommendation of opioids in chronic osteoarthritis pain was analyzed.

Data sources

The databases of Medline, Embase, the Cochrane Library, and the Internet from 1990–2009 were searched.

Study selection

Two independent authors included randomized controlled clinical trials investigating the effects of chronic opioid treatment for the management of osteoarthritis pain. In order to calculate the odds ratio, only placebo-controlled trials were included.

Data extraction

The primary outcome parameter was the dropout rate. Secondarily, the effect size was calculated. Data extraction was conducted by two independent authors.

Results

A total of 19 studies reporting results of 3,871 treatment and 2,080 placebo outcomes were retrieved. Compared to placebo, opioid treatment was associated with a significantly increased total dropout rate (OR=1.3, 95%CI 1.2–1.4). Discontinuation of treatment was related to adverse events (OR=4.0, 95%CI 3.4–4.6). Lack of analgesia was associated with a significantly reduced dropout rate in opioid groups (OR=0.4, 95%CI 0.3–0.5). Analgesic effects were significantly better in opioid-treated patients (p=0.01).

Conclusion

In spite of analgesic effects, many osteoarthritis patients prefer to stop chronic opioid use, because of adverse events. Therefore, opioids are not generally recommended in osteoarthritis.

Zusammenfassung

Hintergrund

Die Interpretation von Opioidstudien bei Patienten mit chronischen Schmerzen bei Arthrose wird durch eine hohe Abbruchrate eingeschränkt. Wir haben untersucht, welche Bedeutung eine differenzierte Analyse der Gründe für Therapieabbrüche für die Empfehlungen zur Opioidtherapie bei Arthroseschmerz hat.

Fragestellung

Ziel der Untersuchung war zu analysieren, wie hoch die Abbruchrate im Rahmen einer Opioidtherapie bei chronischen Schmerzen infolge Arthrose ist.

Datenquellen

Wir führten Recherchen in Medline, Embase, der Cochrane Library sowie im Internet für den Zeitraum 1990–2009 durch.

Studienauswahl

Zwei Autoren wählten unabhängig voneinander randomisierte kontrollierte Studien aus, die die Wirkung von Opioidanalgetika bei chronischen Arthroseschmerzen untersuchten. Wir beschränkten uns auf placebokontrollierte Studien, um ein Odds Ratio berechnen zu können.

Datenextraktion

Der primäre Endpunkt war die Abbruchrate. Sekundär wurde auch die Effektgröße bestimmt. Die Datenextraktion wurde durch zwei Autoren unabhängig voneinander durchgeführt.

Ergebnisse

Wir analysierten 19 Studien, die insgesamt 3871 mit Opioiden behandelte Patienten und 2080 Placebopatienten einschlossen. Verglichen mit Placebo führt die Opioidbehandlung zu einer signifikant höheren Abbruchrate (Odds Ratio [OR] 1,3; 95%-Konfidenzintervall [KI] 1,2–1,4). Diese Therapieabbrüche waren assoziiert mit Nebenwirkungen (OR 4,0; 95%-KI 3,4–4,6). Eine fehlende Schmerzlinderung führte zu einer signifikant niedrigeren Abbruchrate in der Opioidgruppe (OR 0,4; 95%-KI 0,3–0,5). Die durchschnittliche analgetische Wirkung bei mit Opioiden behandelten Patienten war signifikant besser als in der Placebogruppe (p=0,01).

Schlussfolgerung

Trotz der analgetischen Wirkung beenden vielen Patienten eine Schmerztherapie mit Opioiden wegen Nebenwirkungen. Aufgrund der hohen Abbruchrate besteht trotz nachgewiesener Wirkung keine generelle Indikation für eine Opioidtherapie bei Arthrose. Die Ergebnisse sprechen dafür, die Indikation im Einzelfall einer Opioidbehandlung zu stellen und die subjektive Bewertung von Analgesie und Nebenwirkungen auch im Verlauf einer Opioidtherapie zu überprüfen.

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Conflict of interests

MG received honoraria for lectures by MSD Sharp & Dohme, mundipharma GmbH, Sanofi Aventis, Medtronic, Germany. BH received honoraria for lectures from MSD Sharp & Dohme, Novartis, and Pfizer, Germany. MT received honoraria for lectures from MSD Sharp & Dohme, mundipharma GmbH, Pfizer, Germany.

This analysis was not funded.

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Authors and Affiliations

  1. Dept. of Anesthesiology, Intensive Care Medicine and Pain Therapy, Klinikum Kassel GmbH, Moenchebergstr. 41–43, 34125, Kassel, Deutschland

    M. Gehling & M. Tryba

  2. Orthopädische Fachpraxen, Hamburg, Deutschland

    B. Hermann

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  1. M. Gehling
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  2. B. Hermann
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  3. M. Tryba
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Correspondence to M. Gehling.

Additional information

Contribution to the manuscript MG contributed to conception and design, data acquisition, analysis and interpretation, drafting of the manuscript, revision, and statistical analysis. BH contributed to conception and design, data acquisition, analysis and interpretation, drafting of the manuscript, revision, and statistical analysis. MT contributed to conception and design, drafting of the manuscript, revision, and statistical analysis.

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Gehling, M., Hermann, B. & Tryba, M. Meta-analysis of dropout rates in randomized controlled clinical trials. Schmerz 25, 296–305 (2011). https://doi.org/10.1007/s00482-011-1057-9

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