PharmacoEconomics

, Volume 28, Issue 10, pp 935–945 | Cite as

Comparative Effectiveness Without Head-to-Head Trials

A Method for Matching-Adjusted Indirect Comparisons Applied to Psoriasis Treatment with Adalimumab or Etanercept
  • James E. Signorovitch
  • Eric Q. Wu
  • Andrew P. Yu
  • Charles M. Gerrits
  • Evan Kantor
  • Yanjun Bao
  • Shiraz R. Gupta
  • Parvez M. Mulani
Methodological Considerations Comparative Effectiveness Without Head-to-Head Trials

Abstract

The absence of head-to-head trials is a common challenge in comparative effectiveness research and health technology assessment. Indirect cross-trial treatment comparisons are possible, but can be biased by cross-trial differences in patient characteristics. Using only published aggregate data, adjustment for such biases may be impossible. Although individual patient data (IPD) would permit adjustment, they are rarely available for all trials. However, many researchers have the opportunity to access IPD for trials of one treatment, a new drug for example, but only aggregate data for trials of comparator treatments. We propose a method that leverages all available data in this setting by adjusting average patient characteristics in trials with IPD to match those reported for trials without IPD. Treatment outcomes, including continuous, categorical and censored time-to-event outcomes, can then be compared across balanced trial populations.

The proposed method is illustrated by a comparison of adalimumab and etanercept for the treatment of psoriasis. IPD from trials of adalimumab versus placebo (n = 1025) were re-weighted to match the average baseline characteristics reported for a trial of etanercept versus placebo (n = 330). Reweighting was based on the estimated propensity of enrolment in the adalimumab versus etanercept trials. Before matching, patients in the adalimumab trials had lower mean age, greater prevalence of psoriatic arthritis, less prior use of systemic treatment or phototherapy, and a smaller mean percentage of body surface area affected than patients in the etanercept trial. After matching, these and all other available baseline characteristics were well balanced across trials. Symptom improvements of ≥75% and ≥90% (as measured by the Psoriasis Area and Severity Index [PASI] score at week 12) were experienced by an additional 17.2% and 14.8% of adalimumab-treated patients compared with the matched etanercept-treated patients (respectively, both p < 0.001). Mean percentage PASI score improvements frombaseline were also greater for adalimumab than for etanercept at weeks 4, 8 and 12 (all p < 0.05). Matching adjustment ensured that this indirect comparison was not biased by differences in mean baseline characteristics across trials, supporting the conclusion that adalimumab was associated with significantly greater symptom reduction than etanercept for the treatment of moderate to severe psoriasis.

Notes

Acknowledgements

This study was supported by Abbott Laboratories, Inc. and Analysis Group, Inc. Editorial support was provided by Ellen Stoltzfus, PhD, of JK Associates. JES, EQW, APY and EK are employees of Analysis Group, Inc., which received funding for this research from Abbott Laboratories. CMG, YB, SRG and PMM are employees and shareholders of Abbott Laboratories.

Supplementary material

40273_2012_28100935_MOESM1_ESM.pdf (250 kb)
Supplementary material, approximately 255 KB.

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Copyright information

© Adis Data Information BV 2010

Authors and Affiliations

  • James E. Signorovitch
    • 1
  • Eric Q. Wu
    • 1
  • Andrew P. Yu
    • 1
  • Charles M. Gerrits
    • 2
  • Evan Kantor
    • 1
  • Yanjun Bao
    • 2
  • Shiraz R. Gupta
    • 2
  • Parvez M. Mulani
    • 2
  1. 1.Analysis Group Inc.BostonUSA
  2. 2.Abbott LaboratoriesAbbott ParkUSA

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