Medicines Adaptive Pathways to Patients: Why, When, and How to Engage?

Medicines Adaptive Pathways to Patients (MAPPs) seeks to foster access to novel beneficial treatments for the right patient groups at the earliest appropriate time in the product life-span, in a sustainable fashion. We summarize the MAPPs engagement process and critical questions to be asked at each milestone of the product life-span. These considerations are of relevance for regulatory and access pathways that strive to address the "evidence vs. access" conundrum.

Measuring the patient health, societal and economic benefits of US pediatric therapeutics legislation.

Through at least the mid-1990s, children were often referred to as 'therapeutic orphans' for whom many treatments were administered without the benefit of appropriate studies to guide drug labeling for dosing and other critical therapeutic decisions. At that time, there were no incentives for manufacturers to pursue such work, nor regulatory requirements to compel these studies. Congress addressed this by including an important provision titled the Best Pharmaceuticals for Children Act (BPCA) in the 1997 Food and Drug Administration Modernization and Accountability Act. This was complemented by another key piece of legislation, the Pediatric Research Equity Act (PREA) in 2003. The former Act and its successors created an incentive for firms to study on-patent drugs in pediatric populations by extending the market exclusivity of a medicine by 6 months. The latter was a requirement that provided the US FDA with the authority to require studies of drugs in children if an adult indication also occurs in children. In the current paper, we consider the effects of both pieces of legislation in terms of the health, societal, and economic benefits they have likely imparted and will continue to provide in the future. We conclude that the gains have been substantial - both in terms of safer and more effective use of medicines in children and in terms of new research that has been incentivized by the BPCA exclusivity provision. We estimate the gross economic benefits from the latter alone to be approximately $US360 billion.

Recommendations regarding technical standards for follow-on biologics: comparability, similarity, interchangeability.

BACKGROUND: Policy makers around the world are currently considering the creation of a regulatory pathway for follow-on biologics (FOB), which will have to account for the substantial technical challenges associated with FOB development. These challenges will likely involve more complexity than comparability assessments of process changes made by the same manufacturer. The history of industry-regulator comparability discussions helps explain why the same degree of testing and flexibility now applied to change-control within a manufacturer's own process, at this time, cannot be extrapolated to the observed and possibly unknown differences between two manufacturing processes that are independently developed by different (non-collaborating) parties. OBJECTIVES: This commentary provides recommendations on the technical aspects that should be considered in the creation of an approval pathway for FOB products. CONCLUSIONS: In the authors' view, analytical methodology in its current state cannot alone provide full assurance that the FOB is sufficiently similar to the innovator product. Moreover, the FOB manufacturer will not have access to the extensive knowledge accumulated by the innovator manufacturer from early development through marketing. Thus, extensive clinical evaluation will likely be necessary to provide assurance that the FOB is safe and efficacious. If such testing demonstrates the FOB is safe and efficacious per existing regulatory standards, the product should receive marketing approval as a 'similar' product. Since 'similarity' is a fundamentally different determination than establishing interchangeability between the two products, an interchangeability determination must be based on additional testing and market experience to ensure patient safety. Post-marketing surveillance of the FOB should be conducted to ensure that the approved molecule has similar clinical safety and efficacy as the innovator product, prior to any consideration of interchangeability.

Effect of raloxifene on quality of life: a prospective study using the Utian Quality of Life (UQOL) Scale.

OBJECTIVE: The Utian Quality of Life Scale (UQOL) is a new questionnaire used to quantify patient perception of quality of life in postmenopausal women. The current study is the first to use the UQOL in ascertaining treatment effects on quality of life in postmenopausal women. DESIGN: This was a randomized, double-blind, placebo-controlled study of healthy postmenopausal women. Participants were randomized to raloxifene 60 mg/day or placebo. Participants completed the UQOL at baseline, at 3 months, and at the 6-month study endpoint. RESULTS: A total of 74 women (mean age, 55.6 years) were randomized. In the overall population, there were no significant changes from baseline to 6 months within or between treatment groups in any of the domains or total score, although raloxifene was associated with positive changes from baseline in the occupational (P = 0.093) and health (P = 0.055) domains. In women who completed the study, raloxifene was associated with a significant improvement from baseline in the occupational (P = 0.041) and health (P = 0.025) domains and in the total score (P = 0.044), whereas placebo had no effect. There were no statistically significant differences between raloxifene and placebo in any of the domains or total score. CONCLUSION: Although there were no treatment group differences, raloxifene was associated with an improvement from baseline in the occupational and health domains and in the overall score of the UQOL. Larger studies are needed using the UQOL as a primary endpoint to determine whether the positive effects of raloxifene on quality of life observed in this trial are real or a chance finding.