Real-world data from expanded access programmes in health technology assessments: a review of NICE technology appraisals 113 6♦ gathered during the conventional clinical trials but were captured in the expanded access program. Although data from expanded access programs can bridge an evidence gap, HRQoL data should simply have been collected during all stages of clinical development. For safety, the use of registries, post-approval safety studies, or pharmacovigilance during expanded access, is useful to detect infrequently occurring adverse events. Indeed, we identified such an example in TA533, where the compassionate use program led to the identification of a rare but serious adverse event. Overall, the evidence for assessing safety and efficacy should primarily come from regulatory studies and can be synthesized with RWD or other non-randomized sources, such as expanded access programs. Including expanded access can have several advantages, as it can increase sample size, add robustness, inform additional parameters - such as HRQoL - or aid to estimate effects for patients that were excluded from the trial, but were included in the expanded access program. Such patients are generally older and frailer,10,60,61 and thus collecting data in these populations helps to extrapolate results on safety and efficacy found in RCTs. Estimates of resource use parameters that are derived from clinical trials, such as adherence, monitoring, or the number of hospital visits, can even be more distinct from real-world settings. Therefore, expanded access data can play a useful role in informing resource use parameters. Furthermore, modelling resource use requires estimates of a large number of input parameters, such as costs, incidence and also transition parameters that determine the amount of time spent in a disease state. Some of these parameters can only be estimated from studies with lengthy follow-up periods, so that patient or population registries or expanded access programs would be best suited to inform decision making on these model inputs. Finally, trial values may not be sufficiently informative, as they are typically multinational and do not contain data relevant to a particular national health system. The regulatory status of data collection during expanded access programs is a matter of debate.11,12,14,16,50,51 In Europe, individual Member States regulate expanded access programs.5 Different countries may issue conflicting statements that can be at cross with EMA decision making.50 This also resonates in appraisals. For example, we read in the appraisal of cemiplimab for treating metastatic or locally advanced cutaneous squamous cell carcinoma: ‘While formal data collection is not permitted from a regulatory standpoint, the safety of cemiplimab at the flat 350mg dose in a real-world setting will be monitored.’ Manufacturer submission, Safety overview, TA592
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