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Indirect comparisons of therapeutic interventions
Ben Schöttker1, Dagmar Lühmann, Dalila Boulkhemair
1Institut für Sozialmedizin, Universität zu Lübeck, Lübeck, Deutschland.
Indirect comparisons can estimate head-to-head trial results when direct comparisons are unavailable. Adjusted indirect comparisons and Mixed Treatment Comparisons (MTC) offer valid results if study quality is high.
Area of Science:
- Health Technology Assessment (HTA)
- Comparative Effectiveness Research
- Evidence Synthesis
Background:
- Health technology effectiveness comparisons are legally mandated and crucial for clinical guidelines.
- Randomized controlled head-to-head trials are the gold standard but rarely available.
- Indirect comparisons are often necessary but their validity is debated.
Purpose of the Study:
- To identify statistical methods for indirect comparisons of therapeutic interventions.
- To assess the frequency of their application in systematic reviews.
- To evaluate the validity of indirect comparison results against head-to-head trials.
Main Methods:
- Systematic literature search of methodological papers and applications in systematic reviews.
- Qualitative summarization of methods and quantitative analysis of application frequency.
- Validity assessment by comparing indirect results to direct (head-to-head) trial results.
Main Results:
- Four indirect comparison methods identified: unadjusted, adjusted, metaregression, and Mixed Treatment Comparisons (MTC).
- Adjusted indirect comparisons were most common (1999-2008), with increasing MTC use since 2006.
- Unadjusted indirect comparisons showed the highest discrepancy rate (25.5%) compared to direct trials; MTC had the lowest (1.8%).
Conclusions:
- Method selection depends on validity, number of interventions, and study quality/quantity.
- Unadjusted indirect comparisons have low validity; adjusted indirect comparisons and MTC can yield consistent results.
- Adjusted indirect comparisons and MTC are valuable tools for Health Technology Assessment (HTA) and guidelines when direct comparisons are lacking.
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