Table 2.

Evaluation of method used within indirect comparisons submitted to IQWiG and reasons for rejection

Drug substance	Trade name	Method used for indirect comparison		Reasons for rejection by IQWiG
Abirateron acetat	Zytiga	Adjusted indirect comparison	Bucher’s method, pair wise	•Comparator	•Incompleteness of the used study pool
					•Inclusion criteria of the bibliographic search and data used for each population remained unclear
				•Formal	•Different appropriate comparator as determined by G-BA
Aclidinium bromide	Eklira	MTC	Bayesian approach	•Formal	•Data was not presented adequately (outcomes differ from original source, lacking traceability of data, inadequate inclusion of studies etc.)
Aflibercept	Eylea	Unadjusted indirect comparison	Descriptive	•Methodology	•Comparison does not fulfill the requirements of an adjusted indirect comparison
Axitinib	Inlyta	Unadjusted indirect comparison	simulated treatment comparison	•Methodology	•Comparison does not fulfill the requirements of an adjusted indirect comparison
				•Formal	•Description of the simulated comparison (documented in a
					•Program code) was missing
Collagenase clostridium histolyticum	Xiapex	Unadjusted indirect comparison	-	•Formal	•Comparison does not fulfill the requirements of an adjusted indirect comparison
					•Missing common comparator
				•Methodology	•Patient population was not in line with the application population
Dapagliflozina	Forxiga	Adjusted indirect comparison	Bucher’s method, frequentist approach	•Comparator	•Methodological mismatch: study population within the studies used for comparison was not the same as the indication population
				•Methodology	•Different appropriate comparator as determined by G-BA
Fingolimod	Gilenya	MTC	Bayesian approach	•Methodology	•Inconsistencies in the study search and an inadequate population
				•Formal
Ingenolmebutat	Picato	Unadjusted indirect comparison	-	•Methodology	•Comparison does not fulfill the requirements of an adjusted indirect comparison
					•Common comparator was missing
Linagliptin	Trajenta	Adjusted indirect comparison	Bucher’s method	•Comparator	•Different appropriate comparator as determined by G-BA
Perampanel	Fycompa	Adjusted indirect comparison	Bucher’s method	•Comparator •Methodology	•Different appropriate comparator as determined by G-BA •Examination of a part of the population was criticized
Retigabine	Trobalt	MTC	Frequentist approach	•Comparator	•Different appropriate comparator as determined by G-BA
Ticagrelora	Brilique	Adjusted indirect comparison	Bucher’s method, frequentist approach	-	•Missing validity of endpoints, quality of trials and evidence
					•Methodological restrictions for simple adjusted indirect comparison
Telaprevir	Incivo	MTC	Bayesian approach	•Comparator	•Different appropriate comparator as determined by G-BA
				•Methodology	•Adequate data for handling subgroups was missing (interaction test)
Dabrafenib	Tafinlar	Adjusted indirect comparison	Bucher’s method	•Comparator	•Different appropriate comparator as determined by G-BA
Elvitegravir, Cobicistat, Emtricitabin, Tenofovirdisoproxila	Stribild	Adjusted indirect comparison	Frequentist approach	•Methodology	•Patient population and applied transferability of patient data cannot be followed
Fampridin	Fampyra	Unadjusted indirect comparison	-	•Comparator	•Comparison does not fulfill the requirements of an adjusted indirect comparison
					•Patients, who did not receive best supportive care (physiotherapy) are not similar to patients with placebo treatment (Placebo as common comparator)
				•Methodology	•No data considered with appropriate comparator
Lixisenatid	Lyxumia	Adjusted indirect comparison	Bucher’s method, pair wise	•Comparator	•Different appropriate comparator as determined by G-BA in one indication
				•Methodology	•Differences in patient population, common comparator and application of comparators is not as authorized within included trials
Saxagliptin	Onglyza	Adjusted indirect comparison	Frequentist approach	•Methodology	•Use of inadequate patient population and study period
					•Differences in used common comparators
Saxagliptin (new indication)	Onglyza	Adjusted indirect comparison	Frequentist approach	•Comparator	•Different appropriate comparator as determined by G-BA
Saxagliptin/Metformin (new indication)	Komboglyze	Adjusted indirect comparison	Frequentist approach	•Methodology	•Use of inadequate patient population and study period
					•Application of comparators is not as authorized within included trials
Sitagliptin	Januvia, Xelevia	Adjusted indirect comparison	Bucher’s method, pair wise	•Methodology	•Use of inadequate patient population and study period
					•Application of comparators is not as authorized within included trials
				•Formal	•Missing sensitivity analyses
Teriflunomid	Aubagio	Adjusted indirect comparison	Bucher’s method, MTC	•Methodology	•Incomplete study pool
				•Formal	•Heterogeneity of included studies and non consideration of heterogeneity within indirect comparison
Vildagliptina	Galvus, Jalra, Xiliarx	Adjusted indirect comparison	Bucher’s method	•Methodology	•Use of inadequate patient population and study period
					•No statement towards authorization conform patient population
					•Differences in used common comparators

^aIndirect comparison not in all submitted indications.

Sources: [19-78].