Survival analysis of time to reimbursement of novel medicines in five Eurasian countries – Global Health Research and Policy

Report on Methodological Framework for Assessing Access to Novel Medicines in Alignment with Sustainable Development Goals

Study Design: A Framework for Evaluating Progress Towards SDG 3 and SDG 10

This report outlines a retrospective study designed to analyze survival data concerning the public reimbursement of novel medicines. The methodology is fundamentally aligned with the United Nations Sustainable Development Goals, particularly SDG 3 (Good Health and Well-being) and SDG 10 (Reduced Inequalities). By examining the time-to-event outcome of public funding for medicines, the study provides critical insights into achieving universal health coverage (Target 3.8).

The analysis estimates the relative risk of novel medicines receiving public funding in five global leaders of pharmaceutical innovation, thereby exploring factors that either facilitate or impede equitable access to essential health technologies. This directly addresses the goal of reducing inequalities in health outcomes both within and among countries.

Country Selection and Relevance to SDG 9

The selection of countries was strategically focused on major contributors to global pharmaceutical innovation, a key component of SDG 9 (Industry, Innovation, and Infrastructure). The study included:

• The United Kingdom
• France
• Switzerland
• Japan
• China

These Eurasian nations were chosen for their centralized reimbursement decision mechanisms, allowing for comparable analysis. The United States and Germany were excluded due to decentralized systems or immediate reimbursement policies, respectively. The selected countries demonstrate medical innovation performance exceeding expectations for their development levels, making them critical case studies for understanding how innovation translates into public health benefits. The observation period for approved medicines was from January 1, 2018, to December 31, 2023, with reimbursement status tracked until July 1, 2024, ensuring a contemporary analysis of health system responsiveness.

Variables: Measuring Health System Performance and Equity

The study’s variables were chosen to serve as indicators of progress towards achieving universal health coverage and promoting health equity.

1. Primary Variables:
   • Reimbursement Status: A binary outcome indicating whether a novel medicine is covered by public funding. This directly measures the accessibility of innovative treatments for the general population, a cornerstone of SDG 3.
   • Time-to-Reimbursement (TTR): The duration from regulatory approval to a positive public funding decision. This metric quantifies delays in access and highlights systemic inefficiencies that can exacerbate health inequalities (SDG 10).
2. Covariates:
   • Regulatory Pathways: Analysis of accelerated procedures like Priority Review (PR) and Conditional Market Authorization (CMA) assesses how policies designed to fast-track innovation impact public access.
   • Therapeutic Area: Special attention is given to medicines for rare diseases and cancers, areas of high unmet medical need, to evaluate if health systems prioritize treatments for the most vulnerable populations.
   • Local Development and Manufacturing: The study investigates if locally developed medicines or those from domestic companies receive preferential treatment. This links health policy with SDG 9 by exploring the role of local industrial capacity in achieving national health goals.
   • Country and Year Dummies: These are included to control for systemic differences in healthcare infrastructure and policy shifts over time, ensuring a robust analysis of factors influencing equitable access.

Data Sources: Fostering Transparency and Partnership (SDG 17)

In line with SDG 17 (Partnerships for the Goals), which emphasizes the importance of data and accountability, this study relies exclusively on publicly available, official sources. Data on marketing authorization (MA) and reimbursement decisions were systematically collected from:

• National medicines regulatory authorities.
• Official websites of national public funding and reimbursement agencies.

This transparent approach ensures the replicability of the study and promotes accountability in public health governance. Data extraction was conducted in parallel by two researchers to ensure accuracy and reliability, with a consensus process for any discrepancies.

Statistical Analysis: Generating Evidence for Policy Action

The statistical methodology is designed to generate robust evidence to inform policies aimed at strengthening health systems and reducing access delays, contributing directly to the evidence base needed for SDG 3 and SDG 10.

1. Descriptive and Comparative Analysis: Non-parametric tests (Shapiro-Wilk, Brown-Forsythe, Kruskal-Wallis H) were used to compare TTR distributions across countries, identifying national-level disparities in access to innovation.
2. Survival Analysis: Kaplan-Meier (KM) curves and Cox proportional hazards regression models were employed to analyze TTR and identify key determinants. This analysis is crucial for understanding the factors that predict timely and equitable access to novel medicines. The Cox model allows for the adjustment of multiple covariates, providing a nuanced understanding of the complex interplay between medicine characteristics, manufacturer attributes, and regulatory environments.
3. Subgroup and Sensitivity Analyses:
   • Stratified Cox regressions were conducted for each country to identify nation-specific factors associated with TTR, allowing for tailored policy recommendations.
   • A sensitivity analysis was performed on the data from China to account for the institutionalization of its price negotiation system in 2019, thereby enhancing the consistency and validity of the findings.

All analyses were conducted using Stata/MP 17.0 and R version 4.2.2, with a statistical significance threshold of p

1. Which SDGs are addressed or connected to the issues highlighted in the article?

The article’s analysis of public funding and time-to-reimbursement for novel medicines connects to several Sustainable Development Goals (SDGs). The primary focus on health and access to medicine directly links to SDG 3, while its discussion of pharmaceutical innovation and international disparities touches upon SDGs 9 and 10, respectively.

• SDG 3: Good Health and Well-being

  This is the most relevant SDG. The article’s core subject is the accessibility of “novel medicines” through “reimbursement by public funding.” This directly relates to ensuring healthy lives by making advanced medical treatments available and affordable to the public. The study investigates the efficiency of healthcare systems in providing access to new treatments, particularly for serious conditions like “cancers” and “rare diseases (RDs),” which is central to promoting well-being.

• SDG 9: Industry, Innovation, and Infrastructure

  The article focuses on countries selected as “top contributors to global pharmaceutical innovation” and references the “Global Innovation Index.” It analyzes the pathway of innovative products—”novel medicines”—from development and regulatory approval to public access. This connects to fostering innovation and upgrading the technological capabilities of the pharmaceutical industry, as the reimbursement process is a critical final step in the innovation lifecycle that incentivizes further research and development.

• SDG 10: Reduced Inequalities

  The study performs a comparative analysis of reimbursement systems and timelines across five different countries (the UK, France, Switzerland, Japan, and China). By exploring the differences in “Time-to-Reimbursement (TTR)” and factors affecting it in each country, the article implicitly highlights the inequalities in access to the latest medical treatments that exist even among developed and innovating nations. This aligns with the goal of reducing inequalities among countries.

2. What specific targets under those SDGs can be identified based on the article’s content?

Based on the article’s focus, several specific SDG targets can be identified.

• Targets under SDG 3:

  • Target 3.8: Achieve universal health coverage, including financial risk protection, access to quality essential health-care services and access to safe, effective, quality and affordable essential medicines and vaccines for all. The article’s entire premise revolves around this target. The analysis of “reimbursement by public funding” is a direct examination of a mechanism for universal health coverage. A timely and positive reimbursement decision ensures that “novel medicines” become affordable and accessible, protecting patients from prohibitive out-of-pocket costs and providing access to essential healthcare services.
  • Target 3.b: Support the research and development of vaccines and medicines for the communicable and non-communicable diseases that primarily affect developing countries, provide access to affordable essential medicines and vaccines… The article specifically mentions medicines for “cancers” and “rare diseases,” which are major non-communicable diseases. The study of reimbursement systems is crucial for understanding how to provide access to the products of research and development, a key component of this target.

• Target under SDG 9:

  • Target 9.5: Enhance scientific research, upgrade the technological capabilities of industrial sectors in all countries… including… encouraging innovation and substantially increasing the number of research and development workers… and public and private research and development spending. The article investigates the reimbursement landscape in countries recognized for their “medical innovation performances.” An efficient and predictable reimbursement pathway is a powerful incentive for private and public investment in pharmaceutical R&D, thus encouraging the innovation this target aims to foster.

3. Are there any indicators mentioned or implied in the article that can be used to measure progress towards the identified targets?

Yes, the article explicitly defines and uses several quantitative indicators to measure the performance of healthcare systems in providing access to new medicines.

• Indicators for Target 3.8:

  • Time-to-Reimbursement (TTR): This is the primary indicator used in the study. It is explicitly defined as “the length of time from regulatory approval to reimbursement decision-making by public funding.” A shorter TTR indicates faster public access to new, affordable medicines, serving as a direct measure of the efficiency of a country’s universal health coverage system in delivering essential health products.
  • Reimbursement Status by Public Funding: The article defines this as a binary variable (“1” if reimbursed, “0” if not). This indicator measures the proportion of approved novel medicines that are covered by public health insurance. A higher proportion indicates broader coverage of essential health services and better financial risk protection for the population.
  • Survival Rate (Non-reimbursed medicines): The study uses Kaplan-Meier curves to show “survival rates (non-reimbursed medicines as a proportion to the total number of target medicines).” This is an inverse indicator of access, where a lower “survival” rate of non-reimbursed drugs over time signifies better and faster public funding coverage.

• Indicators for Target 9.5:

  • Annual Number of Novel Medicines Approved: The article mentions that the selected countries have a “comparable annual number of novel medicines approved during the observation period.” This number serves as a direct output indicator of successful pharmaceutical innovation and R&D activity within a country or globally.
  • Global Innovation Index Ranking: The article cites the “Global Innovation Index 2019” to justify the selection of countries like Switzerland and to note that the “medical innovation performances of these countries were above the expectations for their levels of development.” This index is a composite indicator that measures a country’s innovation capabilities and results.

4. Create a table with three columns titled ‘SDGs, Targets and Indicators” to present the findings from analyzing the article.

Source: ghrp.biomedcentral.com