Priority Review Voucher
Encyclopedia
The priority review voucher is a prize awarded in the United States to the developer of a treatment for neglected diseases
. The prize was proposed by Duke University
faculty David Ridley, Henry Grabowski, and Jeffrey Moe in their 2006 Health Affairs paper: "Developing Drugs for Developing Countries." In 2007 Senators Sam Brownback
(R-KS) and Sherrod Brown
(D-OH) sponsored an amendment to the Food and Drug Administration
(FDA) Amendments Act of 2007. President George W. Bush
signed the bill in September 2007.
The prize is an incentive for companies to invest in new drugs and vaccines for neglected tropical diseases. A provision of the Food and Drug Administration Amendments Act (HR 3580) awards a transferable “priority review voucher” to any company that obtains approval for a treatment for a neglected tropical disease. Sponsored by Senators Sam Brownback
(R-KS), and Sherrod Brown
(D-OH), this provision adds to the market based incentives available for the development of new medicines for developing world diseases such as malaria, tuberculosis and African sleeping sickness.
Under current Prescription Drug User Fee Act targets, the FDA aims to complete and act upon reviews of priority drugs within six months instead of the standard ten-month review period. Actual FDA review timelines, however, can be longer than the target PDUFA review periods, particularly for new products that haven’t previously been approved. Economists at Duke University, who published on this concept in 2006, estimated that priority review can cut the FDA review process from an average of 18 months down to six months, shortening by as much as a full year the time it takes for the company’s drug to reach the market.
For a company with a top selling drug with a net present value close to $3 billion, the Duke researchers calculated the accelerated approval could be worth over $300 million. At this level, the voucher would be expected to offset the substantial investment and risk required for discovery and development of a new treatment for a neglected disease. If the time saved from gaining a priority review is much shorter, however, the value of the voucher will be significantly less. In fact, in 2006, median standard review times were 12 months, suggesting that a voucher could cut six months from the standard review period.
An intangible benefit of the voucher is the value created for a company if the faster review provides them "first mover advantage," allowing the voucher holder's product to be introduced ahead of a similar, competing product. By taking advantage of existing market forces, patients in the developing world can have faster access to lifesaving products that may not otherwise be developed. And sponsors of neglected disease drugs can be rewarded for their innovations.
Companies that use the voucher will be required to pay a supplemental priority review user fee to ensure that the FDA can recoup the costs incurred by the agency for the faster review. The additional user fee also aims to ensure that the new program will not slow the progress of other products awaiting FDA review.
Amendments Act of 2007.
at the World Economic Forum in Davos in 2008.
and colleagues, calls for creating a $3 billion market for neglected diseases with high burdens, such as malaria, tuberculosis, and HIV/AIDS.
Second, the voucher prize might be too large, if it rewards research which would have been done anyway, or research with low value. Aidan Hollis of the University of Calgary notes that "firms which are developing very profitable products will be rewarded even more". While some treatments for neglected diseases are lucrative, this is generally not the rule, which is why the diseases are neglected.
Third, the voucher prize encourages innovation, but does not pay for access to existing therapies. Funding from governments or foundations might be needed to purchase treatments for poor people. Aidan Hollis of the University of Calgary has commented that the proposal does not address "the access problem, but helps to increase incentives through creating distortions in markets in developed countries".
Fourth, the voucher prize might tie up FDA resources. Fortunately, however, the law includes an extra fee paid by manufacturers to the FDA and requires that voucher bearers provide FDA with a year notice before using a voucher.
Fifth, priority review might not be safe. Priority review should not, however, be confused with accelerated approval or fast track. Priority review does not omit safety or efficacy studies or require approval within a given time frame. It sets a target of 6 rather than 10 months for FDA review. Nevertheless, if the FDA feels pressure to meet deadlines faster, it might be more likely to err. Carpenter and colleagues (2008) report that new molecular entities approved in the two months before the first review deadlines showed a higher rate of postmarketing safety problems than drugs approved at other times. Nardinelli and colleagues (2008) of the FDA, however, wrote that they were not able to replicate the findings and that the findings might be driven by HIV-AIDS therapies. Following the Nardinelli piece, Carpenter acknowledged several errors in their data set and demonstrated errors in the FDA's and Nardinelli's data; Carpenter and colleagues report that the original associations between last-minute approvals and safety problems hold.
Neglected Diseases
The neglected diseases are a group of tropical infections which are especially endemic in low-income populations in developing regions of Africa, Asia, and the Americas. Different organizations define the set of diseases differently...
. The prize was proposed by Duke University
Duke University
Duke University is a private research university located in Durham, North Carolina, United States. Founded by Methodists and Quakers in the present day town of Trinity in 1838, the school moved to Durham in 1892. In 1924, tobacco industrialist James B...
faculty David Ridley, Henry Grabowski, and Jeffrey Moe in their 2006 Health Affairs paper: "Developing Drugs for Developing Countries." In 2007 Senators Sam Brownback
Sam Brownback
Samuel Dale "Sam" Brownback is the 46th and current Governor of Kansas. A member of the Republican Party, he served as a U.S. Senator from Kansas from 1996 to 2011, and as a U.S. Representative for Kansas's 2nd congressional district from 1995 to 1996...
(R-KS) and Sherrod Brown
Sherrod Brown
Sherrod Campbell Brown is the senior United States Senator from Ohio and a member of the Democratic Party. Before his election to the U.S. Senate, he was a member of the United States House of Representatives, representing Ohio's 13th congressional district from 1993 to 2007...
(D-OH) sponsored an amendment to the Food and Drug Administration
Food and Drug Administration
The Food and Drug Administration is an agency of the United States Department of Health and Human Services, one of the United States federal executive departments...
(FDA) Amendments Act of 2007. President George W. Bush
George W. Bush
George Walker Bush is an American politician who served as the 43rd President of the United States, from 2001 to 2009. Before that, he was the 46th Governor of Texas, having served from 1995 to 2000....
signed the bill in September 2007.
Summary
Sam Brownback
Samuel Dale "Sam" Brownback is the 46th and current Governor of Kansas. A member of the Republican Party, he served as a U.S. Senator from Kansas from 1996 to 2011, and as a U.S. Representative for Kansas's 2nd congressional district from 1995 to 1996...
(R-KS), and Sherrod Brown
Sherrod Brown
Sherrod Campbell Brown is the senior United States Senator from Ohio and a member of the Democratic Party. Before his election to the U.S. Senate, he was a member of the United States House of Representatives, representing Ohio's 13th congressional district from 1993 to 2007...
(D-OH), this provision adds to the market based incentives available for the development of new medicines for developing world diseases such as malaria, tuberculosis and African sleeping sickness.
The mechanism
The statute authorizes the FDA to award a priority review voucher to the sponsor (manufacturer) of a newly approved drug or biologic that targets a neglected tropical disease. The provision applies to New Drug Applications (NDAs), Biological License Applications (BLAs) and 505(b)(2) applications. The voucher, which is transferable and can be sold, entitles the bearer to a priority review for another product.Under current Prescription Drug User Fee Act targets, the FDA aims to complete and act upon reviews of priority drugs within six months instead of the standard ten-month review period. Actual FDA review timelines, however, can be longer than the target PDUFA review periods, particularly for new products that haven’t previously been approved. Economists at Duke University, who published on this concept in 2006, estimated that priority review can cut the FDA review process from an average of 18 months down to six months, shortening by as much as a full year the time it takes for the company’s drug to reach the market.
For a company with a top selling drug with a net present value close to $3 billion, the Duke researchers calculated the accelerated approval could be worth over $300 million. At this level, the voucher would be expected to offset the substantial investment and risk required for discovery and development of a new treatment for a neglected disease. If the time saved from gaining a priority review is much shorter, however, the value of the voucher will be significantly less. In fact, in 2006, median standard review times were 12 months, suggesting that a voucher could cut six months from the standard review period.
An intangible benefit of the voucher is the value created for a company if the faster review provides them "first mover advantage," allowing the voucher holder's product to be introduced ahead of a similar, competing product. By taking advantage of existing market forces, patients in the developing world can have faster access to lifesaving products that may not otherwise be developed. And sponsors of neglected disease drugs can be rewarded for their innovations.
Companies that use the voucher will be required to pay a supplemental priority review user fee to ensure that the FDA can recoup the costs incurred by the agency for the faster review. The additional user fee also aims to ensure that the new program will not slow the progress of other products awaiting FDA review.
Diseases targeted
The tropical diseases that will benefit include the following:- TuberculosisTuberculosisTuberculosis, MTB, or TB is a common, and in many cases lethal, infectious disease caused by various strains of mycobacteria, usually Mycobacterium tuberculosis. Tuberculosis usually attacks the lungs but can also affect other parts of the body...
. - MalariaMalariaMalaria is a mosquito-borne infectious disease of humans and other animals caused by eukaryotic protists of the genus Plasmodium. The disease results from the multiplication of Plasmodium parasites within red blood cells, causing symptoms that typically include fever and headache, in severe cases...
. - Blinding trachomaTrachomaTrachoma is an infectious disease causing a characteristic roughening of the inner surface of the eyelids. Also called granular conjunctivitis and Egyptian ophthalmia, it is the leading cause of infectious blindness in the world...
. - Buruli UlcerBuruli ulcerThe Buruli ulcer is an infectious disease caused by Mycobacterium ulcerans. The genus also includes the causative agents of tuberculosis and leprosy...
. - CholeraCholeraCholera is an infection of the small intestine that is caused by the bacterium Vibrio cholerae. The main symptoms are profuse watery diarrhea and vomiting. Transmission occurs primarily by drinking or eating water or food that has been contaminated by the diarrhea of an infected person or the feces...
. - Dengue/dengue haemorrhagic fever.
- DracunculiasisDracunculiasisDracunculiasis , also called guinea worm disease , is a parasitic infection caused by Dracunculus medinensis, a long and very thin nematode . The infection begins when a person drinks stagnant water contaminated with copepods infested by the larvae of the guinea worm...
(guinea-worm disease). - FascioliasisFascioliasisFasciolosis also known as Fascioliasis, Fasciolasis, distomatosis and liver rot, is an important helminth disease caused by two trematodes Fasciola hepatica and Fasciola gigantica. This disease belongs to the plant-borne trematode zoonoses. In Europe, the Americas and Oceania only F...
. - Human African trypanosomiasis.
- LeishmaniasisLeishmaniasisLeishmaniasis is a disease caused by protozoan parasites that belong to the genus Leishmania and is transmitted by the bite of certain species of sand fly...
. - LeprosyLeprosyLeprosy or Hansen's disease is a chronic disease caused by the bacteria Mycobacterium leprae and Mycobacterium lepromatosis. Named after physician Gerhard Armauer Hansen, leprosy is primarily a granulomatous disease of the peripheral nerves and mucosa of the upper respiratory tract; skin lesions...
. - Lymphatic filariasis.
- OnchocerciasisOnchocerciasisOnchocerciasis , also known as river blindness and Robles' disease, is a parasitic disease caused by infection by Onchocerca volvulus, a nematode . Onchocerciasis is the world's second-leading infectious cause of blindness. It is not the nematode, but its endosymbiont, Wolbachia pipientis, that...
. - SchistosomiasisSchistosomiasisSchistosomiasis is a parasitic disease caused by several species of trematodes , a parasitic worm of the genus Schistosoma. Snails often act as an intermediary agent for the infectious diseases until a new human host is found...
. - Soil transmitted helmithiasis.
- YawsYawsYaws is a tropical infection of the skin, bones and joints caused by the spirochete bacterium Treponema pallidum pertenue...
. - Any other infectious disease for which there is no significant market in developed nations and that disproportionately affects poor and marginalized populations.
The amendment
The amendment can be found on page 150 of the Food and Drug AdministrationFood and Drug Administration
The Food and Drug Administration is an agency of the United States Department of Health and Human Services, one of the United States federal executive departments...
Amendments Act of 2007.
News and reaction
Bill GatesBill Gates
William Henry "Bill" Gates III is an American business magnate, investor, philanthropist, and author. Gates is the former CEO and current chairman of Microsoft, the software company he founded with Paul Allen...
at the World Economic Forum in Davos in 2008.
Limitations
First, the voucher prize might be too small. Diseases with incredible burdens might merit more resources. The Advance Market Commitment, proposed by Michael KremerMichael Kremer
Michael Robert Kremer is a development economist and is currently the Gates Professor of Developing Societies at Harvard University. He is a Fellow of the American Academy of Arts and Sciences, a recipient of a MacArthur Fellowship and a Presidential Faculty Fellowship, and was named a Young Global...
and colleagues, calls for creating a $3 billion market for neglected diseases with high burdens, such as malaria, tuberculosis, and HIV/AIDS.
Second, the voucher prize might be too large, if it rewards research which would have been done anyway, or research with low value. Aidan Hollis of the University of Calgary notes that "firms which are developing very profitable products will be rewarded even more". While some treatments for neglected diseases are lucrative, this is generally not the rule, which is why the diseases are neglected.
Third, the voucher prize encourages innovation, but does not pay for access to existing therapies. Funding from governments or foundations might be needed to purchase treatments for poor people. Aidan Hollis of the University of Calgary has commented that the proposal does not address "the access problem, but helps to increase incentives through creating distortions in markets in developed countries".
Fourth, the voucher prize might tie up FDA resources. Fortunately, however, the law includes an extra fee paid by manufacturers to the FDA and requires that voucher bearers provide FDA with a year notice before using a voucher.
Fifth, priority review might not be safe. Priority review should not, however, be confused with accelerated approval or fast track. Priority review does not omit safety or efficacy studies or require approval within a given time frame. It sets a target of 6 rather than 10 months for FDA review. Nevertheless, if the FDA feels pressure to meet deadlines faster, it might be more likely to err. Carpenter and colleagues (2008) report that new molecular entities approved in the two months before the first review deadlines showed a higher rate of postmarketing safety problems than drugs approved at other times. Nardinelli and colleagues (2008) of the FDA, however, wrote that they were not able to replicate the findings and that the findings might be driven by HIV-AIDS therapies. Following the Nardinelli piece, Carpenter acknowledged several errors in their data set and demonstrated errors in the FDA's and Nardinelli's data; Carpenter and colleagues report that the original associations between last-minute approvals and safety problems hold.
Extension to Europe
Writing in The Lancet, David Ridley and Alfonso Calles Sánchez proposed extending the voucher to the European Union. The proposed EU voucher would provide priority regulatory review through the European Medicines Agency, as well as accelerated pricing and reimbursement decisions by EU member states.External links
- Paper co-author David Ridley talks about the priority review voucher at the National Press Club (Begin Video at 21:20) http://www.kaisernetwork.org/health_cast/hcast_index.cfm?create=high_windows&linkid=1&display=detail&hc=1677 — critique of Priority Review Voucher
- BVGH information page on the Priority Review Voucher
- SEC. 524. (21 USC §360n) Text of the amendment