The evolving value assessment of cancer therapies: Results from a modified Delphi study.

The move toward early detection and treatment of cancer presents challenges for value assessment using traditional endpoints. Current cancer management rarely considers the full economic and societal benefits of therapies. Our study used a modified Delphi process to develop principles for defining and assessing value of cancer therapies that aligns with the current trajectory of oncology research and reflects broader notions of value. 24 experts participated in consensus-building activities across 5 months (16 took part in structured interactions, including a survey, plenary sessions, interviews, and off-line discussions, while 8 participated in interviews). Discussion focused on: 1) which oncology-relevant endpoints should be used for assessing treatments for early-stage cancer and access decisions for early-stage treatments, and 2) the importance of additional value components and how these can be integrated in value assessments. The expert group reached consensus on 4 principles in relation to the first area (consider oncology-relevant endpoints other than overall survival; build evidence for endpoints that provide earlier indication of efficacy; develop evidence for the next generation of predictive measures; use managed entry agreements supported by ongoing evidence collection to address decision-maker evidence needs) and 3 principles in relation to the second (routinely use patient reported outcomes in value assessments; assess broad economic impact of new medicines; consider other value aspects of relevance to patients and society).

Opportunities to improve the adoption of health-related quality of life evidence as part of the French Health Technology Assessment process.

OBJECTIVES: Patient's health-related quality of life (HRQoL) is an important outcome measure that is considered by many payers and health technology assessment (HTA) bodies in the evaluation of treatments. We aimed to identify opportunities for HRQoL to be further incorporated into the assessment of the French HTA by comparing three health systems. We put forward recommendations that could bring further innovations to French patients. METHODS: We reviewed methodologies by the French, German and British HTA, and conducted a systematic review of all French (n = 312) and German (n = 175) HTA appraisals from 01 January 2019 to 31 December 2021. We also setup an advisory board of 11 ex-HTA leaders, payers, methodologists, healthcare providers and patient advocates, from France, Britain and Germany, to discuss opportunities to improve acceptance and adoption of HRQoL evidence in France. RESULTS: Our systematic review of HTA appraisals showed a higher HRQoL data rejection rate in France: in > 75% of cases the HRQoL evidence submitted was not accepted for the assessment (usually for methodological reasons, for example, data being considered exploratory; 16-75% of the appraisals mentioned HRQoL evidence, varying by therapeutic area). Overall, we found the French HTA to be more restrictive in its approach than IQWiG. CONCLUSIONS: Based on these findings we articulate collaborative proposals for industry and the HAS to improve acceptance of HRQoL evidence and create a positive feedback loop between HAS and industry along four dimensions (1) patient perception, (2) testing hierarchy, (3) trial design and (4) data collection.

Innovation in Regulatory Science Is Meeting Evolution of Clinical Evidence Generation.

At the turn of the century, the pharmaceutical industry began a transition toward a focus on oncology, rare diseases, and other areas of high unmet need that required a new, more complex approach to drug development. For many of these disease states and novel approaches to therapy, traditional approaches to clinical trial design fall short, and a number of innovative trial designs have emerged. In light of these changes, regulators across the globe are implementing new programs to provide regular development program support, facilitate accelerated access, use real-world data, and use digital tools to improve patients' lives. Emerging market regulators are also focusing on simplifying their regulatory pathways via regional harmonization schemes with varying levels of ambition. These changes in the external environment imply that biopharma regulatory teams need to adapt and evolve, leveraging digital tools, data, and analytics, and positioning themselves as strategic advisors during development.

Formulation development and manufacturing of a gastrin/CCK-2 receptor targeting peptide as an intermediate drug product for a clinical imaging study.

A DOTA-gastrin analogue (APH070) which, when labelled with (111)In, has high affinity for the gastrin/CCK-2 receptor (3nM) and low tumour to kidney ratio in animal models, has been formulated and manufactured for a clinical study. Oxidation of the peptide methionine residue greatly reduces receptor affinity, therefore development work focused on producing a stable intermediate drug product (iDP) whilst ensuring that the formulation, container, closure and manufacturing process did not inhibit the extremely sensitive radiolabelling reaction (itself a source of oxidation). Stress testing revealed that APH070 was stable at 2-8 degrees C at pH 6-9. Addition of an antioxidant (monothioglycerol) to the peptide formulation reduced stability when compared to buffer alone. Use of FluroTec (4023/50) stoppers (rather than FluroTec Plus (4110/40)) increased both the stability and radiolabelling efficiency of APH070. Long term stability (6 months) of the final formulation (1mg/ml APH070 in 0.01 M pH 7.2 phosphate buffer) stored at 5 degrees C in type I glass vials with FluroTec (4023/50) stoppers was 98.6+/-0.2% and 98.4+/-0.1% for upright and inverted samples, respectively. Clinical scale radiolabelling of the final formulation routinely achieves the specification of >85% (111)In-APH070 (unoxidised) stable for up to 2h after dilution with 0.9% w/v saline solution. Specific uptake of the radiopharmaceutical in CCK-2R-expressing AR42J tumours in nude mice has been demonstrated.