The clinical merit of expanded access 47 I ♣ PROLOGUE A critical challenge is determining the extent to which expanded access objectively improves patient outcomes. As expanded access provides patients access to drugs in development, one needs to evaluate the clinical benefit of drugs under development to derive an estimate of the merits of expanded access itself. Understanding the added clinical benefit of expanded access requires an assessment of the clinical benefits of drugs in development and their likelihood of reaching the market. Assessing benefit of investigational drugs is inherently complicated, as, by definition, these drugs are under investigation. Moreover, determining the benefit of access to early-phase investigational drugs is more complicated than determining benefit to drugs in later stages of development. For example, the interpretation of phase II trials is frequently hampered by a lack of randomization, limited patient numbers, different dosing schedules, among others. Expanded access to phase II drugs may be less likely to provide benefit, as many phase II trials do not progress to phase III. Evaluating the clinical merit of drugs under development itself it highly complicated, and evaluating expanded access to said drugs is even more complex. Nonetheless, we will here attempt to derive a proxy measure to evaluate the benefits patients may derive by accessing investigational drugs through expanded access. First, we will look at the probabilities of drugs advancing through phases of clinical development. Throughout the development process, drugs may be discontinued due to an unfavorable benefit/ risk profile. As a result, access to drugs in later stages of development increases the chances of accessing drugs that are more likely to provide benefit. Second, we can estimate the clinical benefit of new drugs based on data derived from clinical trials or cost-effectiveness analyses.We do so by looking at drugs still recently developed for hematologic malignancies, and looking at drugs that have obtained institutionalized reimbursement in the United Kingdom, meaning they are readily available on the market. We take two approaches in assessing clinical benefit of drugs. The first approach involves specialized disease scales, which are designed to estimate a pre-defined level of clinical benefit within a specific disease area, in this case hematology. The other approach employs a universal metric called the quality-adjusted life year (QALY), enabling comparisons of drug benefits across different disease areas. By comparing the benefits of drugs in development, considering the probabilities of drugs advancing to marketing approval, and factoring in the number of access programs or patients within these programs, in this part we will derive a proxy measure of the clinical value of drugs provided through expanded access.
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