European priority review vouchers for neglected disease product development.

INTRODUCTION: Neglected diseases are a significant global health challenge. Encouraging the development of therapeutics and vaccines for these diseases would address an important unmet medical need. We propose a priority review voucher programme for the European Union (EU). The developer of a drug or vaccine for a neglected disease would receive a voucher for accelerated assessment of a different product at the European Medicines Agency (EMA). METHODS: This study uses retrospective observational data to estimate the potential commercial value of the proposed voucher programme using a five-step approach: (1) estimating the time saved in the EMA accelerated regulatory review; (2) gauging time reductions in accelerated pricing and reimbursement decisions by EU member states; (3) selecting 10 high-revenue products launched between 2015 and 2020 representing typical voucher users; (4) analysing IQVIA MIDAS sales data for the selected products and (5) calculating the net present value (NPV) of the voucher based on the 10 products. RESULTS: The accelerated EMA review would reduce regulatory time by an average of 182 days. Additionally, products could save more than a year in many member states through an expedited 120-day pricing and reimbursement review. The estimated NPV of regulatory acceleration by two quarters would be €100 million. In addition, if France, Italy and Spain reviewed pricing and reimbursement in only 120 days, then the value would double. CONCLUSION: An EU voucher estimated at more than €100 million, coupled with a US$100 million counterpart, offers a meaningful incentive for novel product development. However, the voucher programme should be part of a comprehensive strategy for tackling neglected diseases, rather than a standalone solution.

FDA Global Drug Inspections: Surveillance Of Manufacturing Establishments Remains Well Below Pre-COVID-19 Levels.

During the initial phase of the COVID-19 pandemic, the Food and Drug Administration (FDA) halted inspections of most overseas drug manufacturing establishments. Looking at data from the period 2012-22, we observed steep declines in both foreign and domestic inspections in 2020. By 2022, numbers of inspections remained well below prepandemic levels, with a 79 percent decrease in foreign inspections and a 35 percent decline in domestic inspections compared with 2019. There was no corresponding reduction in drug manufacturing or imports. Also, the resources allocated per inspection surged, although the FDA's overall budget and staffing remained steady. Finally, citations rose dramatically, despite all establishments being given advance notice of inspections. The findings of our study underscore the pressing need to explore alternative methods for ensuring drug safety.

Consequences of a shortage and rationing: Evidence from a pediatric vaccine.

Shortages and rationing are common in health care, yet we know little about the consequences. We examine an 18-month shortage of the pediatric Haemophilus Influenzae Type B (Hib) vaccine. Using insurance claims data and variation in shortage exposure across birth cohorts, we find that the shortage reduced uptake of high-value primary doses by 4 percentage points and low-value booster doses by 26 percentage points. This suggests providers largely complied with rationing recommendations. In the long-run, catch-up vaccination occurred but was incomplete: shortage-exposed cohorts were 4 percentage points less likely to have received the ir booster dose years later. We also find that the shortage and rationing caused provider switches, extra provider visits, and negative spillovers to other care.

​US Tropical Disease Priority Review Vouchers: Lessons In Promoting Drug Development And Access.

The COVID-19 global pandemic has devastated lives and economies. It has served as a reminder of how critical it is to invest in preventing and treating infectious diseases. Until the COVID-19 pandemic, the largest US government-sponsored reward for infectious disease drug and vaccine development was the Tropical Disease Priority Review Voucher program. Under this program, the Food and Drug Administration awards a priority review voucher to the sponsor of a new drug or vaccine for tropical infectious diseases. The voucher then can be exchanged for the faster review of one drug. We provide case studies for tropical disease voucher recipients between 2007 and 2018, examine the effects of the voucher program on product innovation and access, and recommend that policy makers protect the voucher program while creating complementary incentives.

A Voucher System To Speed Review Could Promote A New Generation Of Insecticides To Fight Vector-Borne Diseases.

Many in the scientific community are concerned about the potential increase in prevalence of insect-borne diseases such as Chagas disease, Chikungunya, dengue fever, malaria, and Zika in the United States and around the world. Beyond vaccines and drugs to prevent and treat these diseases, a comprehensive approach to fighting these diseases should include control of disease-carrying vectors, such as mosquitoes. Vector-control methods, such as using insecticides to treat bed nets and spray the walls of homes, have prevented millions of deaths from malaria. However, mosquitoes are becoming resistant to insecticides, and no new class of insecticides for vector control has been introduced in decades. We recommend the creation of a new type of incentive for the development and commercialization of safe new insecticides: a Vector Expedited Review Voucher, to be awarded to a sponsor that introduces a novel insecticide for public health use. The voucher could be redeemed to expedite registration of a second, more profitable, product by the US Environmental Protection Agency.

Priorities for the Priority Review Voucher.

The U.S. Congress created the priority review voucher program in 2007 to encourage development of drugs for neglected diseases. Under the voucher program, the developer of a drug for a neglected or rare pediatric disease that is approved by the U.S. Food and Drug Administration receives a bonus priority review voucher for another drug. As of 2016, four vouchers have sold for an average price of $200 million. Recent experience with the voucher program indicates strengths and weaknesses of the program, as well as a need for legislative changes.

Real-World Data: Policy Issues Regarding their Access and Use.

As real-world data (RWD) in health care begin to cross over to the Big Data realms, a panel of health economists was gathered to establish how well the current US policy environment further the goals of RWD and, if not, what can be done to improve matters. This report summarizes these discussions spanning the current US landscape of RWD availability and usefulness, private versus public development of RWD assets, the current inherent bias in terms of access to RWD, and guiding principles in providing quality assessments of new RWD studies. Three main conclusions emerge: (1) a business case is often required to incentivize investments in RWD assets. However, access restrictions for public data assets have failed to generate a proper market for these data and hence may have led to an underinvestment of public RWDs; (2) Very weak empirical evidence exist on for-profit entities misusing public RWD data entities to further their own agendas, which is the basis for supporting access restrictions of public RWD data; and (3) perhaps developing standardized metrics that could flag misuse of RWDs in an efficient way could help quell some of the fear of sharing public RWD assets with for-profit entities. It is hoped that these discussions and conclusions would pave the way for more rigorous and timely debates on the greater availability and accessibility of RWD assets.

The Commercial Market For Priority Review Vouchers.

In 2007 the US Congress created the priority review voucher program to encourage the development of drugs for neglected diseases. Under the program, the developer of a drug that treats a neglected disease receives both a faster review of the drug by the Food and Drug Administration and a voucher for a faster review of a different drug. The developer can sell the voucher. We estimated the commercial value of the voucher using US sales of new treatments approved in the period 2007-09. A third of the commercial value of a voucher comes from capturing market share from competitors, nearly half from the value of earlier sales because of the expedited review, and less than a quarter from lengthening the time between approval and the launch of a generic competitor. We estimate that if only one priority review voucher is available in a year, it will be worth more than $200 million, but if four vouchers are available, the value could fall below $100 million. Congress should be cautious about expanding the voucher program, because increasing the number of vouchers sharply decreases the expected price. Lower voucher prices could undermine the incentive to develop new medicines for neglected diseases.

No Shot: US Vaccine Prices And Shortages.

In 2004 an Institute of Medicine report warned of vaccine shortages, raising concerns about disease outbreaks. More than a decade later, we looked for progress in reducing vaccine shortages. We analyzed data on vaccine sales and shortages reported by practitioners and patients to the Food and Drug Administration and the American Society of Health-System Pharmacists in the period 2004-13. We found that the number of annual vaccine shortages peaked in 2007, when there were shortages of seven vaccines; there were only two shortages in 2013. There were no shortages of vaccines with a mean price per dose greater than $75 during the study period. Furthermore, we found that a 10 percent increase in price was associated with a nearly 1 percent decrease in the probability of a shortage. Government payers should carefully consider the benefits of averting shortages when evaluating prices for vaccines, including older vaccines whose prices have been subject to congressional price caps.

Payments, promotion, and the purple pill.

Understanding competition in the US drug market requires knowing how sensitive demand is to prices. The relevant prices for insured consumers are copayments. There are many studies of copayment elasticity in the health literature, but they are of limited applicability for studies of competition. Because of a paucity of data, such studies typically control for neither competitor copayment nor advertising. Whereas previous studies examined copayment sensitivity when copayments for branded drugs move in unison, this study examines copayment sensitivity when copayments diverge. This study uses unique panel data of insurance copayments and utilization for 77 insurance groups, as well as data on advertising. The results indicate that demand can be much more sensitive to copayment than previously recognized. Manufacturers selling drugs with higher copayments than branded competitors can lose substantial market share. Manufacturers can offset the loss of demand by increasing advertising to physicians, but it is costly.

Introduction of European priority review vouchers to encourage development of new medicines for neglected diseases.

Every year 1 billion people worldwide are affected by traditionally neglected diseases, such as malaria, tuberculosis, leishmaniasis, and lymphatic filariasis, which impose tremendous public health burdens. Governments, foundations, and drug manufacturers have, however, started to support development of new treatments. European Union Member States have been leaders in implementing so-called push mechanisms (payment for drug development) and pull funding (reward for output), such as the advance market commitment, which creates a market for vaccines by guaranteeing prices. We propose an additional step that could be taken to encourage development of medicines for neglected diseases. A priority review voucher scheme, as is already in place in the USA, would reward a manufacturer that developed a new medicine for neglected diseases with a voucher that could be redeemed for priority review of a future medicine, probably a potential blockbuster drug. Unlike the US system a European voucher would also accelerate pricing and reimbursement decisions. This scheme would be likely to provide substantial benefits to voucher holders, society, and public health organisations.

Would greater transparency and uniformity of health care prices benefit poor patients?

President Bush, the World Health Organization, and leading scholars have called for greater price transparency in health care. Prices are transparent when the buyer knows his or her price or knows prices paid by others, in advance. Transparent prices inform consumers of expected costs and reveal when sellers are charging high prices to poor people. Under some conditions, however, price transparency can increase prices paid by the poor, deter business entry in poor markets, reduce competition, lower investment, and mislead if inaccurately measured by a third party. We recommend alternative approaches to lowering prices for the poor and increasing efficiency.

Developing drugs for developing countries.

Infectious and parasitic diseases create enormous health burdens, but because most of the people suffering from these diseases are poor, little is invested in developing treatments. We propose that developers of treatments for neglected diseases receive a "priority review voucher." The voucher could save an average of one year of U.S. Food and Drug Administration (FDA) review and be sold by the developer to the manufacturer of a blockbuster drug. In a well-functioning market, the voucher would speed access to highly valued treatments. Thus, the voucher could benefit consumers in both developing and developed countries at relatively low cost to the taxpayer.

Spending on postapproval drug safety.

Withdrawals of high-profile pharmaceuticals have focused attention on post-approval safety surveillance. There have been no systematic assessments of spending on postapproval safety. We surveyed drug manufacturers regarding safety efforts. Mean spending on postapproval safety per company in 2003 was 56 million dollars (0.3 percent of sales). Assuming a constant safety-to-sales ratio, we estimated that total spending on postapproval safety by the top twenty drug manufacturers was 800 million dollars in 2003. We also examined, using regression analysis, the relationship between the number of safety personnel and the number of initial adverse-event reports. This study offers information for the debate on proposed changes to safety surveillance.

Impact of Medicaid preferred drug lists on therapeutic adherence.

OBJECTIVE: To estimate rates of non-adherence for statins following implementation of a preferred drug list (PDL). STUDY DESIGN: A retrospective cohort study. METHODS: A difference-in-difference-in-difference approach was used to estimate the impact of a PDL on the use of statins in an Alabama Medicaid population. The PDL restricted access to certain branded medications and imposed a monthly prescription limit. The use of restricted drugs was compared with the use of unrestricted drugs in the months before and after the PDL in North Carolina (where there were no such restrictions) and Alabama. Pharmacy data from 2001 to 2005 were used to examine the effect of the Alabama PDL implemented in 2004. RESULTS: Following the PDL in Alabama, Medicaid beneficiaries treated with statins had an 82% higher relative odds of becoming non-adherent with statin therapy compared with North Carolina and with pre-PDL Alabama [odds ratio (OR) 1.82, 95% CI 1.57, 2.11]. Furthermore, patients taking a restricted statin were more likely to be non-adherent than unrestricted patients (OR 1.42, 95% CI 1.12, 1.80). In addition, among Medicaid beneficiaries taking a restricted statin, people aged 65 years or older were more likely to be non-adherent than their younger counterparts after the PDL (OR 1.33, 95% CI 1.02, 1.73). Fifty-one per cent of patients in the Alabama sample were non-adherent with statin therapy after the PDL, compared with 39% before. Non-adherence was 36% in North Carolina in both periods. CONCLUSION: The management of heart disease and high cholesterol are important challenges, especially for low-income patients. Policy makers should be aware that access restrictions can have adverse consequences for patient adherence.

Price differentiation and transparency in the global pharmaceutical marketplace.

Pharmaceutical manufacturers have increased the availability of their products and sometimes increased their own financial returns by charging lower prices outside of the US and by discounting to lower-income patients in the US. Examples include discounted HIV-AIDS drugs in developing countries and pharmaceutical manufacturers' discount cards in the US. Representatives of some international organisations argue that the price reductions are insufficient to make the medications widely available to lower-income patients. The WHO advocates both differential pricing and price transparency. While its efforts are well meaning, this paper identifies six concerns about its methods of comparing the price of a given molecule across manufacturers and across countries. More significantly, the WHO efforts to increase transparency are likely to lead to less price differentiation and less access to innovative pharmaceuticals. An important reason why manufacturers are reluctant to charge lower prices in lower-income countries is that they fear that such low prices will undermine the prices they charge to higher-income consumers. International organisations should not facilitate transparency but should dissuade governments from making price comparisons and basing their prices on those of lower-income countries. Furthermore, they should endeavour to keep low-priced and free drugs in the hands of the low-income consumers for which they were intended.