Targeted combination therapies in oncology: Challenging regulatory frameworks designed for monotherapies in Europe.

The pharmaceutical value chain, including clinical trials, pricing, access, and reimbursement, is designed for classical monotherapies. Although there has been a paradigm shift that increases the relevance of targeted combination therapies (TCTs), regulation and common practice have been slow to adapt. We explored access to 23 TCTs for advanced melanoma and lung cancer as reported by 19 specialists from 17 leading cancer institutions in nine European countries. We find heterogeneous patient access to TCTs between countries, differences in country-specific regulations, and differences in the clinical practice of melanoma and lung cancer. Regulation that is better tailored to the context of combinational therapies can increase equity in access across Europe and promote an evidence-based and authorized use of combinations.

Improving the Affordability of Anticancer Medicines Demands Evidence-Based Policy Solutions.

The high cost of many new anticancer medicines significantly impedes breakthrough discoveries from reaching patients. A commonly heard refrain is that high prices are necessary to compensate for the high costs of research and development (R&D). Yet, there are promising policy proposals aimed at improving affordability without compromising innovation. In seeking new policy solutions, we argue for a shift away from entrenched opinion toward an evidence-based discourse that is grounded in experiments and real-world pilot studies. We offer a novel perspective and practical recommendations on how empirical evidence could and should be gathered to inform evidence-based policy interventions that lead to sustainable medicine prices in oncology.See related article by Franzen et al. (Cancer Res Commun 2022;2:39-47).

Affordable Prices Without Threatening the Oncological R&D Pipeline-An Economic Experiment on Transparency in Price Negotiations.

The high prices of innovative medicines endanger access to care worldwide. Sustainable prices need to be affordable while sufficiently incentivizing research and development (R&D) investments. A proposed solution is increased transparency. Proponents argue that price and R&D cost confidentiality are drivers of high prices. On the contrary, supporters of confidentiality claim that confidentiality enables targeted discounts which make treatments affordable; moreover, pharmaceutical companies argue that R&D investments would suffer with more transparency. Despite the political relevance, limited empirical evidence exists on the effects of transparency regulations. We contribute to fill this gap with an experiment where we replicate the EU pharmaceutical market in a laboratory setting. In a randomized controlled study, we analyzed how participants, 400 students located in four European countries, negotiated in the current system of Price Secrecy in comparison with innovative bargaining settings where either prices only (Price Transparency) or prices and R&D costs (Full Transparency) were made transparent to buyers. We found that Price transparency had no statistically significant effect on average prices or number of patients treated and made R&D investments significantly smaller (-16.86%; P: 0.0024). On the other hand, Full Transparency reduced prices (-26%; P: 0.0004) and held the number of patients constant at the level of Price Secrecy. It produced price convergence between countries with low and high health budgets, and, despite lower prices, had no effect on R&D investments. Our findings provide novel evidence that combining price and R&D cost transparency could be an effective policy to contribute to sustainable medicine prices. See related article by Franzen et al. (Cancer Discov 2022;12:299-302).

Evidence Underlying Policy Proposals for Sustainable Anticancer Drug Prices: A Systematic Review.

Importance: The financial consequences of high-expenditure innovative drugs and the association of these consequences with access to cancer treatment are substantial. With oncology being one of the major spending blocks of care and research, innovative policies are needed to secure the sustainability and accessibility of health care systems. Despite this strong interest, structured approaches are missing to date, and proposals are often based on opinion rather than fact. Objectives: To evaluate an inventory of policies to reduce drug prices at market launch and analyze the quantitative evidence on which these policies are based. Evidence Review: For this systematic review, a literature search of the Ovid MEDLINE, Embase, Business Source Premier, ABI/Inform, World Health Organization, and Organisation for Economic Co-operation and Development databases was conducted for articles published between January 1, 2001, and December 31, 2017. Publications that described proposed policies with a direct or obvious indirect association with pharmaceutical prices at market launch and with relevance to oncology and high-income countries were included. Evidence basis was assessed per article, and quantitative articles were categorized according to time and data use. Main price mechanisms and scored system disruptiveness per proposal were identified. Data were analyzed from January 1, 2018, to January 1, 2019. Findings: Of the 4775 articles screened, 80 were selected, and an inventory of 23 policies to reduce medicine prices was created. Proposals were diverse but mainly applied the strengthening of competition as an underlying mechanism to reduce drug prices. Of the 80 studies, 23 used quantitative models, but existing evidence was insufficient to deduce price effects, especially considering system disruptiveness. The available evidence was used to identify promising proposals for which testing may be beneficial: transparency, delinkage, 2-part pricing, public research, orphan drug reform, and public clinical trials. Conclusions and Relevance: The findings suggest that despite the urgency of the search for proposals that lead to sustainable drug prices, careful and structured testing of proposals is needed because the implications for access to drug treatment can be substantial.

Impact of organ-on-a-chip technology on pharmaceutical R&D costs.

Healthcare systems are faced with the challenge of providing innovative treatments, while shouldering high drug costs that pharmaceutical companies justify by the high costs of R&D. An emergent technology that could transform R&D efficiency is organ-on-a-chip. The technology bridges the gap between preclinical testing and human trials through better predictive models, significantly impacting R&D costs. Here, we present an expert survey on the future role of organ-on-a-chip in drug discovery and its potential quantitative impact. We find that the technology has the potential to reduce R&D costs significantly, driven by changes in direct costs, success rates and the length of the R&D process. Finally, we discuss regulatory challenges to efficiency improvements.