US incentive scheme for neglected diseases: a good idea gone wrong?
BMJ 2014; 349 doi: https://doi.org/10.1136/bmj.g4665 (Published 21 July 2014) Cite this as: BMJ 2014;349:g4665
All rapid responses
Rapid responses are electronic comments to the editor. They enable our users to debate issues raised in articles published on bmj.com. A rapid response is first posted online. If you need the URL (web address) of an individual response, simply click on the response headline and copy the URL from the browser window. A proportion of responses will, after editing, be published online and in the print journal as letters, which are indexed in PubMed. Rapid responses are not indexed in PubMed and they are not journal articles. The BMJ reserves the right to remove responses which are being wilfully misrepresented as published articles or when it is brought to our attention that a response spreads misinformation.
From March 2022, the word limit for rapid responses will be 600 words not including references and author details. We will no longer post responses that exceed this limit.
The word limit for letters selected from posted responses remains 300 words.
The US Scheme for neglected diseases is not a good idea gone wrong but a bad idea bearing the fruits from the seeds which they sow. (1) The key to innovation is the creation of value which will be self-financing and sustainable over the long-term. The US FDA Priority Review Voucher (PRV) can be looked as the value created for the company investing in research and development for drugs to treat neglected diseases.
The Ridely et al estimated that a drug with a net present value of three (3) billion dollars the value of the PRV would be approximately three (3) hundred million dollars.(2) Although this is a great incentive, the problem with this is the incentive can be too small depending on the complexity of the disease or it can be too large for research of low value.(3) Therefore we need to create a model which would not only facilitate research and development but one which would take a holistic view at the process of value creation. The Maurer model of pay as you go can be potentially be looked at being instituted so that research can assessed along the way rather than the end to end approach which currently exists.(4) The advantage of this model would be investors in the research and development process can judiciously monitor their investments and on the other hand it ensures research is just not a political call and it bring to bear stringent mechanisms for decision making.
It should be noted that neglected disease are mainly prevalent in neglected (rural) places. Many businesses are now moving towards unlocking the wealth in rural markets, as Mamta Kanpur aptly puts it: “as challenging as it is to reach rural consumers, just getting to them will not be enough to prosper.” It requires transformational strategies to be sustainable and innovation is required to move away from just research and development of the drug but to the packaging, pricing, distribution and changes in the operational model of the company.(5) Similarly discovering the drug for the disease state is just not enough, if the laws and the incentives do not take a global view of individual disease states and continues in its present format, there would be many more Knights Therapeutics stories to be told.
1. Doshi P. US incentive scheme for neglected diseases: a good idea gone wrong? BMJ 2014; 349 doi: http://dx.doi.org/10.1136/bmj.g4665 (Published 21 July 2014)
2. Ridley, David B., Henry G. Grabowski, and Jeffrey L. Moe. "Developing drugs for developing countries." Health Affairs 25, no. 2 (2006): 313-324.
3. Hollis A. Optional rewards for new drugs for developing countries. Geneva: World Health Organization, 5 April 2005. www.who.int/entity/intellectualproperty/submissions/Submissions.AidanHol....
4. Maurer, Stephen M. "Choosing the right incentive strategy for research and development in neglected diseases." Bulletin of the World Health Organization 84, no. 5 (2006): 376-381.
5. Kapur, Mamta, Sanjay Dawar, and Vineet R. Ahuja. "Unlocking the wealth in rural markets." Harvard business review 92, no. 6 (2014): 113-117.
Competing interests: No competing interests
As a medical humanitarian organisation that has been working to diagnose and treat people suffering from neglected diseases for almost 30 years (1), Médecins Sans Frontières (MSF) understands only too well that the dearth of research & development (R&D) for new tools to treat these diseases is directly attributable to a lack of funding and effective incentives. These diseases affect some of the poorest and most marginalised populations in the world. The imbalance between their medical needs and the availability of suitable medical tools is too often fatal. In spite of representing more than 10% of the global disease burden, over the past decade, less than 3.8% of new drugs approved across the world were indicated for neglected diseases (2). This represents very little progress from the previous decade, especially as it relates to new chemical entities for neglected diseases.
Innovative incentive mechanisms for R&D, including “pull” mechanisms such as the US FDA Priority Review Voucher (PRV), are crucial to spurring innovation in areas lacking the conventional market “pull” of revenue derived from high product prices and high-volume sales.
However, the FDA’s award of a PRV to Knight Therapeutics for a product that Knight neither developed nor manufactures – and which is not easily procured at affordable prices – highlights the shortfalls of the PRV mechanism as currently designed. The PRV’s effectiveness as an incentive for neglected diseases is limited by its failure to ensure it rewards genuine innovation, a lack of obligations to guarantee affordability and patient access to treatments, and administrative restrictions that limit its potential value to innovators and therefore its effectiveness. MSF is urging the US Congress to amend the PRV legislation to ensure that these shortfalls are fixed and the PRV can fulfil its role in stimulating meaningful investments in neglected disease R&D.
Amendments to the PRV legislation are vital to ensuring it delivers benefits to neglected patients, yet even if fixed, the PRV mechanism alone is not enough to address unmet medical needs in the area of neglected diseases. Additional funding, as well as incentives that promote research collaboration and efficiencies, “de-link” the costs of R&D from the price of the end product, and ensure access and the affordability of treatments, should be prioritised. For example, the 3P Project (3), developed by MSF in collaboration with other organisations, would employ an open collaborative R&D framework and a combination of push, pull and pool mechanisms to promote the timely development of more effective treatments for drug-resistant tuberculosis (DR-TB).
MSF calls on the US Congress to amend the PRV mechanism to close loopholes and ensure that benefits reach patients suffering from neglected diseases, and to consider additional mechanisms to incentivise R&D for neglected diseases that ensure all patients needing treatment are able to access the resulting products.
(1) An overview of the current innovation and access challenges MSF faces for NTDs: http://www.msfaccess.org/our-work/neglected-diseases
(2) Pedrique, et al. 'The drug and vaccine landscape for neglected diseases (2000—11): a systematic assessment'. Lancet (2013): http://www.thelancet.com/journals/langlo/article/PIIS2214-109X(13)70078-0/fulltext
(3) 'PUSH, PULL, POOL: Accelerating Innovation and Access to Medicines for Tuberculosis', http://www.msfaccess.org/our-work/driving-medical-innovation/article/2157
Competing interests: No competing interests
US incentive scheme for neglected diseases: a good idea gone wrong? – a response from TDR
We welcome Doshi’s well-balanced analysis of the priority review voucher (PRV), prompted by the licensure of miltefosine in the USA.(1) It raises interesting general issues about incentivising innovation for products to address diseases that would otherwise be neglected due to market failure. This includes diseases which are rare in high-income countries, yet highly prevalent in low- and middle-income countries, and those that affect fractions of societies who cannot afford to pay the prices that would make these drugs attractive for industry.
The problem is hugely complex and there is no obvious easy solution at hand. The goal is to produce affordable health interventions that can get to everyone who needs them. The PRV is a welcome innovation in the R&D process, but as the commentary highlights it is not without its limitations. Indeed, the World Health Organization’s Expert Working Group report (2) and the Consultative Expert Working Group on R &D financing and co-ordination (3) were critical of the PRV scheme for similar reasons to Doshi. Both of these reports also added criticisms of the US based registration system, its failures to open up intellectual property and absence of assurance that the final product will be delivered at an affordable price in the developing world.
The PRV scheme could, indeed should, be improved. Of the three drugs granted the PRV so far, two had already been registered by another demanding regulatory authority outside the USA and were for use in the relevant disease endemic countries. Doshi suggests that the PRV should be reserved for drugs that are first registered in the USA. But in the case of miltefosine, the PRV also failed to increase access to this drug, which is no cheaper now than before the PRV was granted. We suggest that there should be an additional string attached to the scheme that commits the company to make the product in question available at an affordable price in disease endemic countries. We should remember, though, that the PRV alone cannot solve this problem, nor can any other measure in isolation.
Solutions must be systemic, and the public, not-for-profit and for-profit sectors need to work hand in hand. We must collectively think of catalytic transformative changes that involve not only rewards, but also conditions that encourage innovation in neglected areas. Together, all of us must work towards making R&D more efficient and less expensive. This goes beyond a model where the public sector chips in to ‘de-risk’ the process (as TDR did for miltefosine), or a market is created (as is the case for malaria and tuberculosis through the Global Fund for AIDS, Tuberculosis and Malaria, GFATM). Technical solutions are required to improve a development process which is unreasonably long, inefficient, and expensive.
WHO and TDR continue to explore new ways of supporting R&D, including the recent establishment of new projects to demonstrate how R&D can be financed with the final price of the product delinked from the R&D costs. (4) Innovation, so necessary in the discovery and development of new products, also needs to be applied to re-engineer the R&D process so that it can truly address the public health needs of the poorest in our society.
1. Doshi P. US incentive scheme for neglected diseases: a good idea gone wrong? BMJ 2014; 349 doi: http://dx.doi.org/10.1136/bmj.g4665 (Published 21 July 2014)
2. Research and Development. Coordination and Financing. Report of the Expert Working Group. World Health Organization, Geneva (2010). http://www.who.int/phi/documents/RDFinancingEN.pdf?ua=1
3. Research and Development to Meet Health Needs in Developing Countries: Strengthening Global Financing and Coordination Report of the Consultative Expert Working Group on Research and Development: Financing and Coordination. World Health Organization, Geneva (2012) http://www.who.int/phi/cewg_report/en
4. http://www.who.int/phi/implementation/phi_cewg_meeting/en/
Competing interests: No competing interests
Re: US incentive scheme for neglected diseases: a good idea gone wrong?
Dear Editor,
I read with interest the article by P. Doshi about the US incentive scheme for neglected tropical diseases.
I would like to share the following data which I believe could be useful for this discussion.
1. Studies matching six different neglected tropical diseases registered at ClinicalTrials.gov (search date: July 31, 2014).
2. Miltefosin interventional studies in leishmania registered at ClinicalTrials.gov and other registers (collected via WHO ICTRP).
3. Published unregistered clinical trials (single arm and controlled studies) evaluating the effectiveness and safety of miltefosine in patients with leishmania.
Competing interests: - I live in a country well-known as a hot spot of tropical diseases (Colombia) - I endorse the principles of open data in human biomedical research