Summary 251 role in generating reliable evidence. With this in mind, we shift our focus to the practical aspect of statistically integrating these data with regulatory trial information. ♥ Expanded access programs may complement evidence obtained through regulatory trials, but both are frequently analyzed separately. In Part III, we developed a novel statistical technique to incorporate evidence from both data sources simultaneously. By combining Bayesian dynamic borrowing methods with propensity score matching techniques, we attempted to attenuate unmeasured and measured confounding. In a similar fashion to how researchers have aimed to incorporate information on historical control groups into the current trial control arm, we showed that it is possible to incorporate information from current expanded access treatment groups into the current trial treatment arm. We illustrated our method by acquiring and analyzing individual patient-level data of participants in the trial and expanded access program of vemurafenib, a treatment for breast cancer. Where the interpretation of expanded access data had so far been qualitative, now a quantitative tool is available. However, mere access to a tool does not justify its use. Incorporating expanded access data without thoroughly considering the ethical ramifications may lead to regrets or unintended consequences that are difficult to rectify post-hoc, and we examined these concerns in the last Part of this thesis. ♠ The shifting view on expanded access from solely a treatment modality to also a research opportunity raises concerns. To fully leverage expanded access data, and considering that companies, regulators, and payers often rely on and actively seek such data, it is imperative to proactively address a wide range of ethical and practical considerations that are central to the future of expanded access. These considerations include critical aspects such as data quality, clinical development, financial compensation, and research oversight, among others. In Part IV, we clarify the changing role of expanded access from an ethical standpoint, contending that expanded access encompasses both treatment and research. The balance between the advantages of generating evidence and the added burdens of collecting data placed on patients and physicians to conduct research depends in part on the context in which expanded access data are evaluated. Recognizing that the value of such data might be limited compared with conventional clinical trials, it is important to highlight that they can still effectively complement other sources of realworld evidence. We have shown that this is particularly relevant for generating data for academic publications, reimbursement decisions, and providing additional evidence in rare disease contexts.
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