Does global drug innovation correspond to burden of disease? The neglected diseases in developed and developing countries.

Although it is commonly argued that there is a mismatch between drug innovation and disease burden, there is little evidence on the magnitude and direction of such disparities. In this paper, we measure inequality in innovation, by comparing research and development activity with population health and gross domestic product data across 493 therapeutic indications to globally measure: (a) drug innovation, (b) disease burden, and (c) market size. We use concentration curves and indices to assess inequality at two levels: (a) broad disease groups and (b) disease subcategories for both 1990 and 2010. For some top burden disease subcategories (i.e., cardiovascular and circulatory diseases, neoplasms, and musculoskeletal disorders), innovation is disproportionately concentrated in diseases with high disease burden and large market size, whereas for others (i.e., mental and behavioral disorders, neonatal disorders, and neglected tropical diseases) innovation is disproportionately concentrated in low burden diseases. These inequalities persisted over time, suggesting inertia in pharmaceutical research and development in tackling the global health challenges. Our results confirm quantitatively assertions about the mismatch between disease burden and pharmaceutical innovation in both developed and developing countries and highlight the disease areas for which morbidity and mortality remain unaddressed.

Patient-Reported Outcomes and Experiences Assessment in Women with Breast Cancer: Portuguese Case Study.

In 2020, female breast cancer was the most commonly diagnosed cancer worldwide, representing the type of cancer with the highest incidence among women and the second most common cause of cancer death among women in all OECD countries. The conventional measures addressing the burden of breast cancer by measuring mortality, incidence, and survival do not entirely reflect the quality of life and patients experience when receiving breast cancer care. The main objective of this study is to capture patient-reported outcomes and experiences in women with breast cancer in Portugal using methods developed for international benchmarking purposes, such as the OECD Patient-reported Indicators Surveys. The study included 378 women with breast cancer, with the age distribution being 19.8% aged 15 to 49 years and 80.2% aged 50 years and over. The data collection procedure and analysis followed the "OECD Breast Cancer Patient Reported Outcomes Working Group" protocol, allowing subsequent comparability with data from other OECD member countries. Most women were satisfied with the treatment outcome regarding the shape of their lumpectomy breast when wearing a bra (96.1%) and with the equal size of both breasts (78.3%). Findings on the WHO QOL-BREF showed that women manifest a lower score in well-being when compared with the general population or populations living with chronic diseases. This study shows the feasibility of implementing and using patient-reported metrics (PROM and PREM) in breast cancer services in Portugal. Measuring PROMs and PREMs from Portuguese women receiving breast cancer care provides insightful evidence into the quality and value of cancer care.

The Impact of the Priority Review Voucher on Research and Development for Tropical Diseases.

BACKGROUND: In 2007, the priority review voucher (PRV) was implemented in the US to incentivize research and development (R&D) for tropical diseases. The PRV is issued by the US FDA and grants a quicker review to manufacturers upon successful development of a product for a disease eligible for the program. OBJECTIVE: The objective of this analysis was to assess whether the PRV has incentivized R&D (measured as clinical trial activity) for the intended tropical diseases. METHOD: We used a difference-in-difference-in-differences (DDD) strategy by exploiting variation in its implementation across diseases and registries around the world. Clinical trials were retrieved from the World Health Organization International Clinical Trials Registry Platform for the years 2005-2019. RESULTS: We found a positive, but not statistically significant, effect of the PRV on stimulating R&D activity. Delayed effects of the policy could not be found. CONCLUSION: Our findings, which were robust across a series of robustness tests, suggest that the PRV program is not associated with a trigger in innovation for neglected diseases and therefore should not be considered as a stand-alone solution. It should be supplemented with other government measures to incentivize R&D activity. To increase the value of the program, we recommend that the PRV only be awarded to novel products and not to products that have already been licensed outside the US. Doing so would restrict the number of vouchers awarded and slow down their ongoing market depreciation. Finally, we propose that product sponsors be required to submit an access plan for PRV-awarded products.

Inequities in cancer drug development in terms of unmet medical need.

This study measures inequality and inequity in the distribution of clinical trials on cancer drug development between 1996 and 2016, comparing the number of clinical trials with cancer need, proxied by prevalence, incidence, or survival rates for both rare and non-rare cancers. We leverage a unique global database of clinical trials activity and costs between 1996 and 2016, constructed for 227 different cancer types to measure for rare and non-rare cancers: i) inequalities and inequity of clinical trial activity, considering all trials as well as split by R&D stage; ii) inequalities and inequity in R&D investment proxied by trial enrollment and duration; iii) evolution of inequity over time. Inequalities are measured with concentration curves and indices and inequities measured with the health inequity index. We find four important results. First, we show pro-low need inequity across cancer types for both rare and non-rare cancers, for all need proxies. Second, we show inequity differs across R&D stages and between rare and non-rare cancers. The distribution of clinical trials for non-rare cancers disproportionately favors low-need non-rare cancers from earlier to later stages of R&D, whilst for rare cancers this only occurs in Phase 2 trials. Third, inequity analyses in R&D investment show that only trial enrollment for rare cancers and trial duration for non-rare cancers are disproportionately concentrated among low-need cancers. Finally, while pro-low need inequity has persisted between 1996 and 2016 for non-rare cancers, it has faded for rare cancers post-EU orphan drugs' legislation.

The importance of surgeons and their peers in adoption and diffusion of innovation: An observational study of laparoscopic colectomy adoption and diffusion in England.

Little is known about the role of clinicians in accounting for adoption and diffusion of medical innovations, especially within the English National Health System. This study examines the importance of surgical consultants and their work-based networks on the diffusion of an important innovation, minimally invasive elective laparoscopic colectomy for colorectal cancer. The study used linked patient-level and workforce data on 260,110 elective colectomies and 1288 consultants between 2000 and 2014, to examine adoption of laparoscopic colectomy pre- and post-introduction of clinical guidelines and total share of colectomies performed laparoscopically by adopters. Laparoscopy as a share of elective colectomy increased from 0% in 2000 to 53% in 2014. Surgeons, rather than hospitals, were the principal agents accounting for the increase and explain 46.6% of the variance in laparoscopic colectomy use. Female surgeons, surgeons trained outside the United Kingdom, and recent graduates had higher rates of laparoscopy adoption. More experienced surgeons and surgeons with more peers who perform laparoscopy were more likely to adopt, adopt early and have greater use of laparoscopy. Targeting clinicians, rather than hospitals, is central to increasing adoption and diffusion of new medical technologies.

Vertical and horizontal equity of funding for malaria control: a global multisource funding analysis for 2006-2010.

BACKGROUND: International and domestic funding for malaria is critically important to achieve the Sustainable Development Goals. Its equitable distribution is key in ensuring that the available, scarce, resources are deployed efficiently for improved progress and a sustained response that enables eradication. METHODS: We used concentration curves and concentration indices to assess inequalities in malaria funding by different donors across countries, measuring both horizontal and vertical equity. Horizontal equity assesses whether funding is distributed in proportion to health needs, whereas vertical equity examines whether unequal economic needs are addressed by appropriately unequal funding. We computed the Health Inequity Index and the Kakwani Index to assess the former and the latter, respectively. We used data from the World Bank, Global Fund, Unicef, President's Malaria Initiative and the Malaria Atlas Project to assess the distribution of funding against need for 94 countries. National gross domestic product per capita was used as a proxy for economic need and 'population-at-risk' for health need. FINDINGS: The level and direction of inequity varies across funding sources. Unicef and the President's Malaria Initiative were the most horizontally inequitable (pro-poor). Inequity as shown by the Health Inequity Index for Unicef decreased from -0.40 (P<0.05) in 2006 to -0.25 (P<0.10) in 2008, and increased again to -0.58 (P<0.01) in 2009. For President's Malaria Initiative, it increased from -0.19 (P>0.10) in 2006 to -0.38 (P<0.05) in 2008, and decreased to -0.36 (P<0.10) in 2010. Domestic funding was inequitable (pro-rich) with inequity increasing from 0.28 (P<0.01) in 2006 to 0.39 (P<0.01) in 2009, and then decreasing to 0.22 (P<0.10) in 2010. Funding from the World Bank and the Global Fund was distributed proportionally according to need. In terms of vertical inequity, all sources were progressive: Unicef and the President's Malaria Initiative were the most progressive with the Kakwani Indices ranging from -0.97 (P<0.01) to -1.29 (P<0.01), and -0.90 (P<0.01) to -1.10 (P<0.01), respectively. CONCLUSION: Our results suggest that external funding of malaria treatment tends to be allocated to countries with higher health and economic need but not in proportion to their relative health need and income when compared to other countries. While malaria eradication might require funders to disproportionally allocate funding that goes beyond (financial and health) need, our analysis highlights that funders might potentially be targeting in excess certain countries. Regular assessments of need and greater coordination among donors are necessary for equitable resource allocation, to improve and sustain progress with malaria control and elimination.