Table 2 Evaluation of method used within indirect comparisons submitted to IQWiG and reasons for rejection

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

Dapagliflozin^a

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

Ticagrelor^a

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, Tenofovirdisoproxil^a

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

Vildagliptin^a

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