Methodological problems in the use of indirect comparisons for evaluating healthcare interventions: survey of published systematic reviews.
OBJECTIVE
To investigate basic assumptions and other methodological problems in the application of indirect comparison in systematic reviews of competing healthcare interventions.


METHODS
Survey of published systematic reviews. Inclusion criteria Systematic reviews published between 2000 and 2007 in which an indirect approach had been explicitly used.


METHODS
Identified reviews were assessed for comprehensiveness of the literature search, method for indirect comparison, and whether assumptions about similarity and consistency were explicitly mentioned.


RESULTS
The survey included 88 review reports. In 13 reviews, indirect comparison was informal. Results from different trials were naively compared without using a common control in six reviews. Adjusted indirect comparison was usually done using classic frequentist methods (n=49) or more complex methods (n=18). The key assumption of trial similarity was explicitly mentioned in only 40 of the 88 reviews. The consistency assumption was not explicit in most cases where direct and indirect evidence were compared or combined (18/30). Evidence from head to head comparison trials was not systematically searched for or not included in nine cases.


CONCLUSIONS
Identified methodological problems were an unclear understanding of underlying assumptions, inappropriate search and selection of relevant trials, use of inappropriate or flawed methods, lack of objective and validated methods to assess or improve trial similarity, and inadequate comparison or inappropriate combination of direct and indirect evidence. Adequate understanding of basic assumptions underlying indirect and mixed treatment comparison is crucial to resolve these methodological problems. APPENDIX 1: PubMed search strategy. APPENDIX 2: Characteristics of identified reports. APPENDIX 3: Identified studies. References of included studies.
Song
Fujian
F
Faculty of Health, University of East Anglia, Norwich NR4 7TJ. fujian.song@uea.ac.uk
Loke
Yoon K
YK
Walsh
Tanya
T
Glenny
Anne-Marie
AM
Eastwood
Alison J
AJ
Altman
Douglas G
DG
D003695:Delivery of Health Care / Q000592:standards*; D005069:Evaluation Studies as Topic; D006801:Humans; D015201:Meta-Analysis as Topic; D016032:Randomized Controlled Trials as Topic / Q000379:methods; D012107:Research Design; D012196:Review Literature as Topic