Background
Methods
Identification and inclusion of benefit assessments
Identification and inclusion of EPARs and PAMs
Classification of therapeutic indication
Quality of data from RCTs for oncology drugs with conditional vs. unconditional appraisals
Categories of missing data
-
Efficacy: efficacy data or specific efficacy endpoint(s) explicitly mentioned in the EPAR or the G-BA decision rationale and/or request listed in the ‘conclusions on clinical efficacy’ section of the EPAR; data from (randomised) studies
-
Safety: safety data or specific safety endpoint(s) explicitly mentioned in the EPAR or the G-BA decision rationale and/or request listed in the ‘conclusions on clinical safety’ section of the EPAR; data from safety studies (randomised or observational studies or registries)
-
Effectiveness: data from non-interventional, observational or 'real-life' studies or registries other than for the purposes of safety monitoring, or requests for data on representative patient populations covering the entire indication
-
Pharmacology: data on drug-drug interactions, pharmacokinetics, pharmacodynamics, dosing or dose timing
-
Reference to EMA (only applicable for G-BA requests): Data requests consistent with PAM(s)
Types of data requested
-
RCT: data from RCTs
-
Non-RCT: data from non-randomised studies
-
Analysis: new analyses of existing data or ongoing studies
-
Other: e.g. simulations or in vitro studies
-
Reference to EMA (only applicable for G-BA requests): data requests consistent with PAMs
Main topics in G-BA data requests beyond EMA data requirements
-
Endpoint: Data on specific endpoints either not presented by manufacturer or not accepted by the G-BA
-
Comparator: (Direct) comparison to the appropriate G-BA-specified comparator missing
-
Long-term data: Data on long-term outcomes missing
-
Patient number: Number of patients for a specific population too small
-
Population: Further subdivision of population requested
-
Post-marketing safety concerns (specific to safety requests): Safety concerns due to safety signals from post-marketing experience
-
Incomplete population (specific to effectiveness requests): Study population not reflecting the full indication
-
Population not representative (specific to effectiveness requests): Study population not comparable to patients treated in the German context
Data extraction procedure
Results
Analysis set
Product | Brand name | Indication | Conditional appraisalsd
| PAMse
| ||
---|---|---|---|---|---|---|
y/n | Time frame (years) | Number | Time frame (years) | |||
Aclidinium bromide | Eklira Genuair/Bretaris Genuair | COPD | No | - | 1 | n.a. |
Afatinib | Giotrif | Non-small-cell lung carcinoma | Yes | 1 | 0 | - |
Afliberceptf
| Zaltrap | Metastatic colorectal cancer | No | - | 1 | 4 |
Afliberceptf
| Eylea | Age-related macular degeneration | No | - | 1 | 5 |
Aliskiren/amlopidine | Rasilamlo | Essential hypertension | No | - | 2 | 1; n.a. |
Axitinib | Inlyta | Renal cell carcinoma | Yes | 4 | 0 | - |
Belatacept | Nulojix | Renal transplantation | Yes | 3 | 0 | - |
Belimumab | Benlysta | Systemic lupus erythematodes | No | - | 3 | 1.5; 8.5; 11.5 |
Boceprevir | Victrelis | Chronic hepatitis C | No | - | 1 | 4.5 |
Bosutinibg,c
| Bosulif | Chronic myeloid leukaemia | Yes | 5 | 2 | 1; 5.5 |
Brentuximab vedoting,c
| Adcetris | Hodgkin lymphoma, anaplastic large-cell lymphoma | No | - | 4 | Annually; 3.5; 3.5; 6 |
Crizotinibc
| Xalkori | Non-small-cell lung carcinoma | Yes | 2 | 2 | 1.5; 3.5 |
Dabrafenib | Tafinlar | Melanoma | Yes | 3.5 | 0 | - |
Elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil | Stribild | HIV infection | No | - | 1 | 0.5 |
Emtricitabine/rilpivirine/tenofovir disoproxilh
| Eviplera | HIV infection | No | - | 2 | 1; 2 |
Eribulin | Halaven | Breast cancer | Yes | 2 | 0 | - |
Extract of Cannabis sativa
| Sativex | Multiple sclerosis | Yes | 3 | No centralised procedure | |
Fampridinec
| Fampyra | Multiple sclerosis | No | - | 1 | 5.5 |
Fidaxomicin | Dificlir | Infection with clostridium | No | - | 2 | 1.5; 1.5 |
Fingolimod | Gilenya | Multiple sclerosis | Yes | 3 | 1 | 9.5 |
Fluticasone furoate/vilanterol trifenatate | Relvar Ellipta | Asthma, COPD | No | - | 2 | 2; 2.5 |
Indacaterol/glycopyrronium | Ultibro Breezhaler, Xoterna Breezhaler | COPD | No | - | 1 | 5 |
Ipilimumabi
| Yervoy | Melanoma (pre-treated) | Yes | 5 | 1 | 6 |
Ipilimumab (new indication)i
| Yervoy | Melanoma (treatment-naïve) | Yes | 3.5 | 1 | 6 |
Ivacaftorg
| Kalydeco | Cystic fibrosis | No | - | 2 | 3.5; 5.5 |
Lixisenatide | Lyxumia | Diabetes mellitus type 2 | No | - | 1 | 1.5 |
Lomitapidec
| Lojuxta | Hypercholesterolaemia | Yes | 1 | 2 | Annually; 6.5 |
Ocriplasmin | Jetrea | Vitreomacular traction | Yes | 5 | 0 | - |
Pertuzumab | Perjeta | Breast cancer | Yes | 5 | 2 | 3.5; 4.5 |
Pirfenidoneg
| Esbriet | Idiopathic pulmonary fibrosis | No | - | 1 | 6.5 |
Pixantronec
| Pixuvri | Non-Hodgkin lymphoma | No | - | 1 | 3 |
Pomalidomideg
| Imnovid | Multiple myeloma | No | - | 2 | 1; 7 |
Ponatinibg
| Iclusig | Lymphoblastic leukaemia, myeloid leukaemia | Yes | 1 | 0 | - |
Regorafenib | Stivarga | Colorectal cancer | Yes | 1.5 | 5 | 0.2; 0.2; 1; 2; 7.5 |
Rilpivirineh
| Edurant | HIV infection | No | - | 2 | 1; 2 |
Ruxolitinibg
| Jakavi | Chronic myeloproliferative disorders | No | - | 2 | Annually; 1 |
Saxagliptin/metformin | Komboglyze | Diabetes mellitus type 2 | Yes | 2 | 0 | - |
Tafamidis meglumineg,c
| Vyndaqel | Amyloidosis | No | - | 1 | annually |
Ticagrelor | Brilique | Acute coronary syndrome | No | - | 1 | 2.5 |
Trastuzumab emtansine | Kadcyla | Breast cancer | No | - | 3 | 1; 3; 3.5 |
Vandetanibj,c
| Caprelsa | Thyroid neoplasms | Yes | 3 | 2 | 2; 4 |
Vemurafenib | Zelboraf | Melanoma | Yes | 1 | 1 | 2 |
Vismodegibc
| Erivedge | Basal cell carcinoma | Yes | 2 | 2 | 1; 2 |
Therapeutic indications
Quality of data from RCTs for oncology drugs
Conditional appraisals (N = 12) | Unconditional appraisals (N = 9) | Total (N = 21) | |
---|---|---|---|
Number of RCTs presented in manufacturer’s dossier (mean ± SD) | 1.3 ± 1.2 | 1.0 ± 0.5 | 1.2 ± 1.0 |
Number of patients in largest RCT (mean ± SD) | 577 ± 207 | 939 ± 361 | 729 ± 329 |
Number of control arms (mean ± SD) | 1.1 ± 0.3 | 1.0 ± 0 | 1.1 ± 0.2 |
Use of an active control (n, %) | 8 (67 %) | 3 (33 %) | 11 (52 %) |
Benefit outcome influenced by potential for bias | 8 (67 %) | 1 (11 %) | 9 (43 %) |
Direct comparison to appropriate comparator available | 9 (75 %) | 7 (78 %) | 16 (76 %) |
Categories of missing data
Conditional appraisals (N = 35 categories)
n
b
| PAMs (N = 54 categories)
n
b
| |
---|---|---|
Category | ||
Efficacy | 13 | 22 |
Safety | 10 | 22 |
Effectiveness | 5 | 2 |
Pharmacology | 0 | 8 |
Reference to EMAc
| 7 | – |
Types of data requested
Type of non-RCT PAM |
n
|
---|---|
Drug interaction and PK studies | 7 |
Post-authorisation safety studies | 5 |
Single-arm studies | 4 |
Long-term observational or non-interventional studies | 3 |
Registries | 2 |
Cohort studies | 2 |
Other | 1 |
G-BA data requests beyond EMA data requirements
Efficacy | Safety | Effectiveness |
---|---|---|
Endpoint [8] | Comparator [5] | Incomplete population [3] |
Comparator [4] | Endpoint [2] | Population not representative [2] |
Long-term data [4] | Long-term data [2] | |
Patient number [1] | Post-marketing safety concerns [2] | |
Population [1] | Patient number [1] | |
Population [1] |