Innovations in pharmaceutical policies and learnings for sustainable access to affordable medicines.

Sustainable access to affordable medicines remains a public health issue globally, including for high-income countries. To foster the debate on avenues for the future, the fifth PPRI Conference held in Vienna on 25 and 26 April 2024 will offer a forum for the debate on innovating pharmaceutical policymaking to develop and implement futureproof policy options, which are able to address current and future challenges. The Conference invites a broad audience of stakeholders, including researchers, policymakers, payers, patients, industry and health professionals. The conference topics are organised in three strands: Strand 1 on 'Local challenges, global learnings' aims to contribute to lively discussions on the implementation of pharmaceutical policies across the globe. Best-practice examples will be presented, supplemented by case studies of less effective policies which can offer rich learnings. Strand 2 on 'Strengthening the evidence base' is the place for presentations and discussions on topics such as health technology assessments, managed entry agreements and real-world data. Strand 3 'Futureproofing pharmaceutical policies' is particularly dedicated to explore innovation in policymaking to achieve sustainable access to affordable medicines.

Tiered Pricing and Alternative Mechanisms for Equitative Access to Vaccines in Latin America: A Narrative Review of the Literature.

OBJECTIVES: To review and describe alternative strategies for the supply of vaccines in Latin America. METHODS: We conducted a narrative review to explore and describe alternatives for equitable vaccine access in Latin America. We searched and considered the main access strategies reported in the literature through PubMed, Science Direct, and Google Scholar. Additionally, we reviewed the web sites of key stakeholders. The search was conducted using the following keywords: ("access" or "availability" or "acquisition" or "affordability" or "tiered pricing") and ("vaccine"). Subsequently, documents that met the inclusion criteria were selected. Finally, findings were grouped by means of a thematic analysis and an interpretative synthesis. RESULTS: Twenty-four publications were included. We identified 5 main topics: current supply strategies, challenges for the acquisition of vaccines, vaccine prices equity, alternative supply strategies, and the advantages and impact of a tiered pricing strategy. CONCLUSIONS: Our review suggests that tiered pricing can be an tool for accelerating the process of introducing vaccines in low-income countries at affordable prices and for countries that do not adhere to the current procurement mechanisms or are not eligible for Vaccine Alliance because giving countries prices for vaccines that reflect their ability to pay can result in better programmatic and financial planning for the purchase of these vaccines, and in return, vaccine manufacturers can gain access to wider markets However, this model has not been z improve access to vaccines that are aimed only at developing countries, mainly because the market in these countries is not profitable for producers.

Convined clinical prognostic model in colorectal cancer.

Current staging systems in patients with colorectal cancer (CRC) utilize relatively few patient characteristics in comparison to the breadth of information available. The objective of our study is to analyze the heterogeneous set of variables that may influence mortality and recurrence independently in patients with CCR, and prepare a predictive model of survival and recurrence. Data from 288 patients who had undergone scheduled surgery for stage I-III cancer of the colon and upper rectum were used to construct Cox models for DFS and overall CSS at five years. We have jointly examined clinical variables, serological markers and histological variables with the aim of identifying new prognostic factors. Internal and external validation was carried out on each of the nomograms obtained. Perineural invasion; high platelet-lymphocyte ratio (PLR) and the pN stage were the variables that emerged as an independent risk factor of recurrence. The variables related independently to overall CSS were the presence of blood in stools, high PLR and nodal involvement. We have created a predictive model of recurrence and mortality at 5 years with data that is easily available (clinical, analytical and histological variables) which can help personalize the treatment and follow-up of patients with CRC. We also conducted an adequate internal and external validation.

The Efficiency of Increased HCV Testing and Treatment Strategies in Spain to Achieve Elimination Goals.

BACKGROUND: In 2015, Spain launched a national eradication strategy for hepatitis C virus (HCV), resulting in the highest treatment rate in Europe and substantial reductions in HCV prevalence. However, to achieve the goal of HCV elimination, it is necessary to scale-up the diagnosis, treatment, and management of HCV infection. OBJECTIVE: Our aim was to assess the prevalence, incidence, and cost effectiveness of scaling-up compared with status quo scenarios. METHODS: A compartmental dynamic transmission model was developed comprising of a cascade of care and a liver progression module. Cost and quality-of-life inputs were sourced from the literature. Key outcomes were the prevalence and incidence of HCV and the incremental cost per quality-adjusted life-year (QALY) and per life-year (LY). Outcomes for a hypothetical elimination strategy were compared with the status quo. RESULTS: The base-case analysis found that scaling-up testing and treatment reduced both the prevalence and incidence of HCV over time, resulting in incremental costs per QALY and LY of €13,291 and €12,285 respectively, compared with the status quo. The main drivers of the cost-effectiveness results included cost of diagnosis, cost of treatment, proportion of people who are unaware, percentage of population who inject drugs, and calibration parameters related to HCV infection prevalence. CONCLUSIONS: This analysis demonstrated that scaling-up testing and treatment with direct-acting antivirals may be an efficient strategy for reducing the incidence and prevalence of HCV and may help achieve HCV elimination goals in Spain.

Pricing and reimbursement mechanisms for advanced therapy medicinal products in 20 countries.

Introduction: Advanced Therapy Medicinal Products are a type of therapies that, in some cases, hold great potential for patients without an effective current therapeutic approach but they also present multiple challenges to payers. While there are many theoretical papers on pricing and reimbursement (P&R) options, original empirical research is very scarce. This paper aims to provide a comprehensive international review of regulatory and P&R decisions taken for all ATMPs with centralized European marketing authorization in March 2022. Methods: A survey was distributed in July 2022 to representatives of 46 countries. Results: Responses were received from 20 countries out of 46 (43.5%). 14 countries reimbursed at least one ATMP. Six countries in this survey reimbursed no ATMPs. Conclusion: Access to ATMPs is uneven across the countries included in this study. This arises from regulatory differences, commercial decisions by marketing authorization holders, and the divergent assessment processes and criteria applied by payers. Moving towards greater equality of access will require cooperation between countries and stakeholders, for example, through the WHO Regional Office for Europe's Access to Novel Medicines Platform.

Clinical Outcomes of First-line Therapies for Advanced Non-Small Cell Lung Cancer: A Systematic Review of Trials Published Between 2010 and 2020.

OBJECTIVES: To analyze the evolution of clinical outcomes derived from clinical trials on first-line therapies for advanced or metastatic non-small cell lung cancer (NSCLC) published between 2010 and 2020, focusing on how these outcomes impact survival rates and management of patients. METHODS: A systematic review of phase III and pivotal phase II clinical trials was conducted by a structured search on Medline and Embase. A comprehensive set of variables was collected to assess their influence on survival rates. We also estimated the clinical benefit by applying the ESMO-MCBS v1.1 and extracted the authors' conclusions. RESULTS: Sixty-six studies involving 34,951 patients were included. Best survival outcomes were found for nonsquamous non-small cell lung cancer (OS and progression-free survival medians: 19.4 and 10.2 mo) and for those expressing molecular targets (OS and progression-free survival medians: 23.8 and 11.0 mo). No significant influence on survival rates was observed for industry funding and disease stage (IIIB/IV vs. IV). ESMO-MCBS v1.1 was applied in 45 positive studies and resulted in a meaningful clinical benefit score in 37.8%. Quality of life (QoL) was reported in 57.6% of the original publications and showed statistical significance favoring the experimental arm in 33.3%. Positive authors' conclusions (75.7% of trials) were based on OS and/or QoL in 34% and on surrogate endpoints in 66%. CONCLUSIONS: Extended survival times and a steady improvement in QoL have been observed. However, there were more than twice as many studies reporting positive authors' conclusions as studies meeting the ESMO threshold for meaningful clinical benefit.

Secretion of Interleukin 6 in Human Skeletal Muscle Cultures Depends on Ca2+ Signalling.

The systemic effects of physical activity are mediated by the release of IL-6 and other myokines from contracting muscle. Although the release of IL-6 from muscle has been extensively studied, the information on the cellular mechanisms is fragmentary and scarce, especially regarding the role of Ca2+ signals. The aim of this study was to characterize the role of the main components of Ca2+ signals in human skeletal muscle cells during IL-6 secretion stimulated by the Ca2+ mobilizing agonist ATP. Primary cultures were prepared from surgical samples, fluorescence microscopy was used to evaluate the Ca2+ signals and the stimulated release of IL-6 into the medium was determined using ELISA. Intracellular calcium chelator Bapta, low extracellular calcium and the Ca2+ channels blocker La3+ reduced the ATP-stimulated, but not the basal secretion. Secretion was inhibited by blockers of L-type (nifedipine, verapamil), T-type (NNC55-0396) and Orai1 (Synta66) Ca2+ channels and by silencing Orai1 expression. The same effect was achieved with inhibitors of ryanodine receptors (ryanodine, dantrolene) and IP3 receptors (xestospongin C, 2-APB, caffeine). Inhibitors of calmodulin (calmidazolium) and calcineurin (FK506) also decreased secretion. IL-6 transcription in response to ATP was not affected by Bapta or by the T channel blocker. Our results prove that ATP-stimulated IL-6 secretion is mediated at the post-transcriptional level by Ca2+ signals, including the mobilization of calcium stores, the activation of store-operated Ca2+ entry, and the subsequent activation of voltage-operated Ca2+ channels and calmodulin/calcineurin pathways.

How are health technology assessment bodies responding to the assessment challenges posed by cell and gene therapy?

BACKGROUND: The aims of this research were to provide a better understanding of the specific evidence needs for assessment of clinical and cost-effectiveness of cell and gene therapies, and to explore the extent that the relevant categories of evidence are considered in health technology assessment (HTA) processes. METHODS: A targeted literature review was conducted to identify the specific categories of evidence relevant to the assessment of these therapies. Forty-six HTA reports for 9 products in 10 cell and gene therapy indications across 8 jurisdictions were analysed to determine the extent to which various items of evidence were considered. RESULTS: The items to which the HTA bodies reacted positively were: treatment was for a rare disease or serious condition, lack of alternative therapies, evidence indicating substantial health gains, and when alternative payment models could be agreed. The items to which they reacted negatively were: use of unvalidated surrogate endpoints, single arm trials without an adequately matched alternative therapy, inadequate reporting of adverse consequences and risks, short length of follow-up in clinical trials, extrapolating to long-term outcomes, and uncertainty around the economic estimates. CONCLUSIONS: The consideration by HTA bodies of evidence relating to the particular features of cell and gene therapies is variable. Several suggestions are made for addressing the assessment challenges posed by these therapies. Jurisdictions conducting HTAs of these therapies can consider whether these suggestions could be incorporated within their existing approach through strengthening deliberative decision-making or performing additional analyses.

Review and Assessment of Policy Options for Improving Access to Combination Therapies in Oncology in Europe.

OBJECTIVES: Combinations of on-patent therapies (CTs) are increasingly common in oncology. They cause challenges for funding and affordability, and hence patient access, especially when constituent therapies are owned by different manufacturers. The aim of our study was to develop policy proposals for the assessment, pricing, and funding of CTs and identify which might be relevant in different European countries. METHODS: Following a review of available literature, seven hypothetical policy proposals were developed and subsequently assessed through 19 semi-structured interviews with health policy, pricing, technology assessment and legal experts in seven European countries to identify those most likely to gain traction. RESULTS: Experts saw a need for agreed approaches within a country to manage affordability and funding challenges for CTs. Changes to health technology assessment (HTA) and funding models were considered unlikely, but other policy proposals were seen as mostly useful, with country-specific adaptations. Bilateral discussions between manufacturers and payers were deemed important, and less challenging and protracted than arbitrated dialogue between manufacturers. Usage-specific pricing, possibly using weighted average prices, was considered a prerequisite for the financial management of CTs. CONCLUSIONS: There is a growing need to ensure that CTs are affordable to health systems. It would appear that there is no one set of policies that is appropriate for all countries in Europe, so countries wishing to ensure that patients have (or continue to have) access to CTs of value to them must explore and implement the policies that are best suited to their general approach to funding health care and to the assessment and reimbursement of medicines.