The factors behind the growing importance of RWE Beyond the need to study product utilisation and to keep studying the outcomes of a product after it is commercialised , several key factors have driven the broadened use of RWE 2 and will be further explored below . These include :
• Increased complexity of pharmaceutical innovations
• High budget impact associated with new therapies
• Lack of generalisability of RCTs .
Increased complexity Medical innovations that are addressing high unmet needs reach healthcare stakeholders at an increased pace , thus increasing complexity both for medical practice that incorporates them and for the management of these innovations by the other stakeholders . In oncology , there is a proliferation of treatment options and a fragmentation of patient populations that are challenging to identify for HCPs , and for whom the choice of the right option may also be more complex . Collecting observational data on these groups and treatments delivers RWE that helps reduce uncertainty . Regulators have set up accelerated approval pathways for innovative treatments addressing unmet needs often for life-threatening conditions , that patients , HCPs and the society are demanding early , such as for COVID-19 vaccines and treatments . Regulators accept these innovations with a higher degree of uncertainty based on the commitment to produce more post-approval data , most of it being RWE . Payers are struggling both with high prices and with the uncertainty stemming from this flow of innovations for which only RCT data – even limited data based on accelerated approval – do not allow them to know the true value in routine care . This is particularly acute for orphan drugs , or gene and cell therapies . There can be significant discrepancies between the results of RCTs and the real-life outcomes of product utilisation . Payers need the precious ‘ effectiveness ’ data coming from RWE to reduce uncertainty . This is why we have seen an explosion of more complex pricing and reimbursement contracts between payers and pharma manufacturers that link the price of new pharmaceuticals with real-life outcomes , or conditions a price to the production of RWE . 2
Generalisability issues with RCTs Traditionally , Health Technology Assessment ( HTA ) bodies , that assess the added value of new drugs relative to already existing alternatives to support decisions on funding and pricing , have relied on evidence generated from RCTs . However , RCT protocols contain extensive inclusion and exclusion criteria in order to avoid bias and increase internal validity and robustness . These strict eligibility criteria often excluding populations of certain age , disease stage or with comorbidities 3 means that the results of RCTs do not always translate to the real-world population in terms of both drug safety and effectiveness . In other terms , the generalisability of RCT populations to general populations , or ‘ external validity ’ is often low . As payers require that manufacturers demonstrate the value of their new drugs , they also want to know if the results from clinical studies will translate to the real-world target population . 4 This has presented an opportunity for RWE to close the evidence gap that exists between clinical trials and real-world populations providing a need for companies to generate RWE from a market access standpoint . 2
Efficacy and effectiveness The two complementary concepts of efficacy and effectiveness reflect the divide between RCTs and RWE . Efficacy is the answer to the “ can it work ?” question , asked and addressed under RCT conditions , whereas effectiveness is the answer to the question “ does it actually work ?” under real life conditions and addressed with RWE .
Healthcare economics In addition , payers want to know what the budgetary impacts of pharmaceutical interventions are ; in other words , what is the overall cost or saving associated with treatment using a new intervention compared to treatments that are currently available , and what are the various cost components ? RCTs are far from ideal to conduct such observations because most of the costs are ‘ protocol-induced ’, meaning that the type and amount of healthcare resources
4 | 2021 | hospitalpharmacyeurope . com