Accelerating the Drug Delivery Pipeline for Acute and Chronic Pancreatitis

Abstract

Recurrent acute pancreatitis (RAP) is a complex clinical syndrome with significant morbidity, unpredictable outcomes and limited treatment options. The National Institute of Diabetes and Digestive and Kidney Disease sponsored a workshop on July 25, 2018 in Pittsburgh, PA to address research gaps impeding development of effective therapies for pancreatitis. The RAP working group identified challenges to clinical progress using existing definitions, risk assessment, diagnostic and severity criteria, disease trajectories, outcomes and research methods. RAP includes all the risk of acute pancreatitis (AP) and often progresses to chronic pancreatitis (CP) with variable complications of chronic pain, exocrine insufficiency, diabetes and pancreatic cancer. However, the great variability among individuals with RAP requites better precision in defining the risks, individual episodes and their frequency, pathogenic pathways and specific outcome measures for each of the systems affected by pancreatic inflammation. Because of disease complexity, few patients are similar enough for traditional studies and methods to conduct clinical trials with small sample sizes are required. The need for genetic testing, biomarker development and better imaging methods was highlighted. Adaptive and N-of-one study designs, better endpoints and outcome measures including patient reported outcomes should considered early in developing future therapeutic trial design and include all stakeholders.

Clinical Trials in Pancreatitis: Opportunities and Challenges in the Design and Conduct of Patient-Focused Clinical Trials in Recurrent Acute and Chronic Pancreatitis

“…There are currently no US Food and Drug Administration (FDA)–approved therapies for the treatment of AP, RAP, or CP. Recognizing this unmet clinical need, the National Institute of Diabetes and Digestive and Kidney Diseases of the National Institutes of Health (NIH) sponsored a workshop on July 20, 2022, entitled, “Clinical Trials in Pancreatitis: Opportunities and Challenges in the Design and Conduct of Patient-Focused Clinical Trials in Recurrent Acute and Chronic Pancreatitis.” This builds on previous work from a related workshop in 2018 (“Accelerating the Drug Delivery Pipeline for Acute and Chronic Pancreatitis: Knowledge Gaps and Research Opportunities”) 1,2 …”

“…There are important regulatory considerations for drug development in RAP and CP 2 . In 1962, Congress amended the Federal Food, Drug, and Cosmetic Act to add a requirement that, to obtain marketing approval, manufacturers demonstrate the effectiveness of their products through the conduct of adequate and well-controlled trials.…”

“…There are important regulatory considerations for drug development in RAP and CP. 2 In 1962, Congress amended the Federal Food, Drug, and Cosmetic Act to add a requirement that, to obtain marketing approval, manufacturers demonstrate the effectiveness of their products through the conduct of adequate and wellcontrolled trials. Adequate and well-controlled trials include a clear statement of objectives, appropriate control for comparison, selection of patients with the disease or who are at risk of developing the disease, methods to minimize bias, well-defined and reliable methods for assessment of response, and adequate methods of analysis.…”

“…This builds on previous work from a related workshop in 2018 ("Accelerating the Drug Delivery Pipeline for Acute and Chronic Pancreatitis: Knowledge Gaps and Research Opportunities"). 1,2 Recurrent AP and CP were selected as the focus of the current workshop because of the significant overlap in both clinical manifestations of disease and potential therapeutic targets between the conditions. The goals of the workshop were to convene key stakeholders including representatives from patient advocacy organizations, physician investigators (including clinical trialists), the FDA, and the NIH to promote collaboration and identify knowledge gaps and challenges to the design and conduct of clinical trials of RAP and CP and opportunities to advance the development of safe and effective therapies for patients.…”