The legalization of cannabinoid products and standardizing cannabis-drug development in the United States: a brief report

This brief report covers recent advances in cannabis and cannabinoid regulation and drug approval. The popularity of cannabis and cannabinoid products continues to rise, and these products are available for the majority of the population in the United States to purchase as easily as alcohol. Although many states have approved programs and research licenses, these activities and products all remain federally illegal. The solution may be for the United States to offer multiple pathways for product approval that adapt to the diversity of the products and the needs of the consumer. Multiple pathways for market approval would protect public health, whether the public is using cannabis and cannabinoids as a medicine, a wellness product, or as a recreational substance.

Predicting Regulatory Product Approvals Using a Proposed Quantitative Version of FDA’s Benefit–Risk Framework to Calculate Net-Benefit Score and Benefit–Risk Ratio

Background Approval of regulated medical products in the USA is based upon a rigorous review of the benefits and risks as performed by the US Food and Drug Administration (FDA) staff of scientists and is summarized in a descriptive and qualitative format called the FDA’s Benefit–Risk Framework (BRF). This present method highlights the key factors in regulatory decision-making, but does not clearly define the reason for its final approval. Method This study proposes a quantitative version of FDA’s BRF to calculate a Net-Benefit Score and a Benefit–Risk Ratio as a method to define a single-value summary of the tradeoffs between benefits and risks and allow comparisons among other products. In this retrospective review of five years of new molecular entities and new biologic (N = 185 products) regulatory decision-making, this proposed scoring system codifies and quantitates the information about a product’s benefits, risks, and risk management information in a format that may predict why regulated medical products are approved in the USA. Results Simple calculation of codified benefits, risks, and risk mitigations with numerical limits is proposed to provide a repeatable process and transparency for documenting the net-benefit of regulatory product approval. Conclusion Use of a strict process of collecting, codifying, and analyzing public information to determine a Net-Benefit score and a Benefit–Risk Ratio is possible to anticipate regulatory product approval.

Adaptive design clinical trials: a review of the literature and ClinicalTrials.gov

ObjectivesThis review investigates characteristics of implemented adaptive design clinical trials and provides examples of regulatory experience with such trials.DesignReview of adaptive design clinical trials in EMBASE, PubMed, Cochrane Registry of Controlled Clinical Trials, Web of Science and ClinicalTrials.gov. Phase I and seamless Phase I/II trials were excluded. Variables extracted from trials included basic study characteristics, adaptive design features, size and use of independent data monitoring committees (DMCs) and blinded interim analyses. We also examined use of the adaptive trials in new drug submissions to the Food and Drug Administration (FDA) and European Medicines Agency (EMA) and recorded regulators’ experiences with adaptive designs.Results142 studies met inclusion criteria. There has been a recent growth in publicly reported use of adaptive designs among researchers around the world. The most frequently appearing types of adaptations were seamless Phase II/III (57%), group sequential (21%), biomarker adaptive (20%), and adaptive dose-finding designs (16%). About one-third (32%) of trials reported an independent DMC, while 6% reported blinded interim analysis. We found that 9% of adaptive trials were used for FDA product approval consideration, and 12% were used for EMA product approval consideration. International regulators had mixed experiences with adaptive trials. Many product applications with adaptive trials had extensive correspondence between drug sponsors and regulators regarding the adaptive designs, in some cases with regulators requiring revisions or alterations to research designs.ConclusionsWider use of adaptive designs will necessitate new drug application sponsors to engage with regulatory scientists during planning and conduct of the trials. Investigators need to more consistently report protections intended to preserve confidentiality and minimise potential operational bias during interim analysis.