Table 1 List of variables extracted
General Information | |
Variable | Description |
Molecule name | International Non-proprietary Name (INN) of medicine |
Brand name | Company branded name of marketed medicine |
Therapeutic indication | Approved therapeutic label of marketed medicine, designating the intended and authorised use of a medicine in a specific patient population. For the included molecules, all approved therapeutic indications recorded from each regulatory agency (FDA, EMA, Health Canada, TGA) |
Regulatory Variables | |
Variable | Description |
Marketing authorisation date | The approval date for marketing authorisation of a specific medicine—indication pair (dd/mm/yyyy). Recorded for each regulatory agency across all included medicine—indication pairs |
Marketing authorisation type | The type of marketing authorisation granted for a specific medicine—indication pair. Categorised as standard approval, priority review, or conditional authorisation. Standard approval includes FDA standard approval, EMA standard approval, TGA standard approval and Health Canada notice of compliance (NOC). Priority review includes FDA priority review, EMA accelerated assessment, TGA priority review, and Health Canada priority review. Conditional authorisation includes FDA accelerated approval, EMA conditional marketing authorisation, TGA provisional approval, and Health Canada, notice of compliance with conditions (NOC/C) |
Orphan designation | Medicine – therapeutic indication received an orphan designation by relevant regulatory agency (0 = no, 1 = yes). Orphan designations indicate the therapeutic indication applies to a rare or orphan disease patient population. Orphan designation criteria vary across settings. The EMA and TGA orphan designations requires a prevalence of less than 5 in 10,000. The FDA orphan designation requires that the condition affects less than 200,000 in the USA. Health Canada does not have an orphan designation |
Clinical Variables | |
Variable | Description |
Study design of pivotal trial | The study design of the pivotal trial used to support conditional regulatory approval. Study designs are classified according to study phase (phase I, phase II, phase III, phase IV, or N/A for non-interventional studies), study blinding (open label or double blind), randomisation (randomised or non-randomised/single arm), and comparators (placebo controlled, actively controlled or uncontrolled) |
Pivotal trial size | The number of patients enrolled in the pivotal trial |
Pivotal trial initiation date | The initiation date of the pivotal trial (per clinicaltrials.gov) |
Type of primary endpoint | The type of primary endpoint used within the pivotal trial (0 = surrogate endpoint, 1 = clinical endpoint). Surrogate endpoints provide an indication or prediction of clinical benefit and provide early signals of a medicines efficacy. The following endpoints have been classified as surrogate within this study: progression free survival (PFS), overall response rate (ORR), subependymal giant cell astrocytoma (SEGA) volume, angiomyolipoma response rate, best observed response (BOR), Primary response (PR), Spleen volume reduction, remission free survival (RFS), complete response rate (CR), duration of response (DOR), major cytogenic response (MCyR), major molecular response (MMR) best-corrected visual acuity (BCVA), forced vital capcity (FVC). Clinical endpoints are hard clinical outcomes that provide an objective measure of clinical benefit. The following endpoints have been classified as clinical within this study: overall survival (OS), maintenance of vision, and seizure frequency |
Primary endpoint outcome | The performance of the primary endpoint defined based on the trial protocol. Includes performance of active arm, performance of control arm, hazard ratio, confidence intervals, and significance (p value). For oncology indications, primary endpoints are predominantly either median progression-free survival (months) or median overall survival (months) |
MCBS Score | The magnitude of clinical benefit scale (per www.esmo.org/guidelines/esmo-mcbs). The MCBS scale is 5 category ranking scale outlining the strength of evidence from 1 (low benefit) to 5 (high benefit). A ranking of 4 or 5 indicates substantial magnitude of benefit. The scale is based predominantly based on the performance of the primary endpoint, and is adjusted for quality of life improvements or changes in toxicity |
HTA variables | |
Variable | Description |
HTA Outcome | HTA outcomes are classified as List (L), List with conditions (LWC), Do not list (DNL), or No HTA submission. In Germany, the G-BA added benefit ratings determine pricing, rather than the listing of a drug. We classify “lesser benefit” or “no proof of added benefit” ratings as DNL, “Proof of major or significant added benefit” as L, and all other ratings as LWC. Note that medicines with lesser or no proof of added benefit may still be reimbursed in Germany based on reference pricing. In France, the medical service rendered (SMR) rating determines the rate of reimbursement, while the improvement in medical service rendered (ASMR) determines pricing. We classify medicines with an SMR of insufficient as DNL, medicines with an SMR of Important and an ASMR of Major or Important as L, and all other ratings as LWC |
HTA recommendation date | The HTA coverage recommendation date (dd/mm/yyyy) |
HTA submission date | The date in which manufacturers filed their submission for health technology assessment. Only available for NICE, SMC and CADTH |