Original article
The results of direct and indirect treatment comparisons in meta-analysis of randomized controlled trials

https://doi.org/10.1016/S0895-4356(97)00049-8Get rights and content

Abstract

When little or no data directly comparing two treatments are available, investigators often rely on indirect comparisons from studies testing the treatments against a control or placebo. One approach to indirect comparison is to pool findings from the active treatment arms of the original controlled trials. This approach offers no advantage over a comparison of observational study data and is prone to bias.

We present an alternative model that evaluates the differences between treatment and placebo in two sets of clinical trials, and preserves the randomization of the originally assigned patient groups. We apply the method to data on sulphamethoxazole-trimethoprim or dapsone/pyrimethamine as prophylaxis against Pneumocystis carinii, in HIV infected patients. The indirect comparison showed substantial increased benefit from the former (odds ratio 0.37, 95% CI 0.21 to 0.65), while direct comparisons from randomized trials suggests a much smaller difference (risk ratio 0.64, 95% CI 0.45 to 0.90; p-value for difference of effect = 0.11).

Direct comparisons of treatments should be sought. When direct comparisons are unavailable, indirect comparison meta-analysis should evaluate the magnitude of treatment effects across studies, recognizing the limited strength of inference.

References (29)

  • TL Nielsen et al.

    Randomized study of sulphamethoxazole-trimethoprim versus aerosolized pentamidine for secondary prophylaxis of Pneumocystis carinii pneumonia in patients with the acquired immunodeficiency syndrome

    Scand J Infectious Dis

    (1995)
  • C Michelet et al.

    Cotrimoxazole versus aerosolized pentamidine for primary prophylaxis of Pneumocystis carinii pneumonia

  • R Stellini et al.

    Trimethoprim-sulphamethoxazole versus pyrimethamine in the primary prophylaxis of toxoplasmic encephalitis in HIV positive patients: Preliminary results of a randomized prospective study

  • DE Smith et al.

    Patient tolerance of nebulized pentamidine or cotrimoxazole as secondary prophylaxis for Pneumocystis carinii pneumonia

    AIDS

    (1992)
  • Cited by (1561)

    • Network meta-analysis: The way forward for evidence-based decisions

      2024, Clinical Epidemiology and Global Health
    View all citing articles on Scopus
    1

    Dr. Bucher was supported by a grant from the Swiss National Research Foundation (grant number 32-38793.93).

    2

    Dr. Walter holds a National Health Scientist award from Health Canada.

    View full text