By STEVEN ZECOLA

Most people would agree that the number of cures for debilitating and costly illnesses such as Alzheimer’s disease, Parkinson’s disease and cancer have been too few and far between.

To address this issue, the U.S. House of Representatives recently passed the 21st Century Cures Act, which now resides in the U.S. Senate for action.  The main thrusts of the Act are to increase government funding for research and to improve several regulatory processes.

Unfortunately, the Act does not address the root cause of the dearth of cures; namely, the inhospitable investment climate for research and development (“R&D”) culminating in the “Valley of Death” for most health-related discoveries.

II. Overview of the 21st Century Cures Act

The 21st Century Cures Act mandates a 3% real increase in the NIH budget per year for three years after enactment. It also provides an additional $1.86 billion a year in the form of an “innovation” fund that would primarily support young scientists and precision medicine.

The bill also provides for changes to the current approval processes including provisions for making data from NIH-funded clinical trials more easily available to researchers, facilitating collaborative research, speeding up the review of new vaccines by the Advisory Committee on Immunization Practices, requiring a strategic plan every five years to identify research opportunities and strategic focus areas, reducing administrative burdens on researchers, and limiting the term of office of directors of centers and institutes to five years (with reappointment by the NIH director possible). The bill also requires the directors of each institute to “establish programs to conduct or support research projects that pursue innovative approaches to major contemporary challenges in biomedical research that involve inherent high risk, but have the potential to lead to breakthroughs” and “set aside a specific percentage of funding, to be determined by the Director of NIH for each national research institute, for such projects.”

III. Critique of the Act

While the provisions of the 21st Century Cures Act are admirable, the Act does not address the underlying reason for the dearth of cures.  That is, the regulatory process adds excessive and unpredictable risk, cost, and delays to research and development that result in a “Valley of Death” where most scientific discoveries remain unfunded.

An approach to overcome this obstacle is summarized here and explained in more detail in a position paper posted at www.thevalleyofdeath.info .  In a nutshell, Congress needs to create an environment that provides for increased incentive for private capital formation to fund R&D without compromising consumer safety.

IV. Summary of Proposed Amendment to Address the Valley of Death in Research and Development

The following five provisions summarize the approach to improve private capital formation for research and development in health-related initiatives.

To ease any concerns between the balance of benefits and public safety with this program, the following recommendations could be rolled out in one or two areas such as Alzheimer’s disease, Parkinson’s disease and/or metastatic cancer where patients have more suffering and less hope for a cure.

The proposed approach is as follows:

1) Congress would limit the FDA’s role in preclinical research to surveillance.

2) Each pre-approved, qualified professional research organization filing a Phase 1 drug application would receive a provisional license from the FDA within 60 days from the time it provided the details of its trial and put a corresponding deposit into an escrow account.

Likewise, applications for Phase 2 and Phase 3 trials would also be subject to a 60 day review cycle and would require additional funds to be deposited into an escrow account, the amount of which would be subject to the size of the trials. A sample deposit schedule follows:

Phase 1 – $250,000 per trial participant
Phase 2-  $100,000 per trial participant
Phase 3 –   $50,000 per trial participant

The above schedule would produce escrowed deposits as follows:

Number of Participants       Incremental Deposit   Cumulative Deposit
Phase 1 20 – 40                       $5M – $10M                 $5M – $10M
Phase 2 100 – 200                   $10M – $20M                $15M -$30M
Phase 3 1000 – 3000                $50M – $150M             $65M – $180M

The FDA would have the authority to reduce the above deposits for special considerations.

3) An industry organization would be required to provide regular reports to the FDA for purposes of oversight (along with the reports provided by individual research organizations with the results of each phase of its trial). This industry organization would have the authority and responsibility to audit individual trial results and to maintain a secure whistle blower system.  A reward would be paid to whistle blowers whose efforts led to the successful prosecution of fraud by a licensee.

4) The FDA would have authority to seek injunctions from the U.S. Court of Appeals to stop any new drug, procedure or device that it believed was unfit for human application.  If a company were found to be in violation of the FDA’s safety guidelines, the company would lose its license and forfeit its escrowed funds.

5) Research organizations would be required to maintain and submit relevant health statistics on patients for one year from commercial launch.  Sixty days after such filings, the FDA would issue a commercial license and the escrowed funds would be returned to the licensee if a Court had not granted an injunction.

Likewise, if the research organization voluntarily abandoned its program during development, the deposit would also be refunded.

Such an approach would place the risk, pace and costs of both pre-clinical research and clinical trials principally under the control of qualified research organizations.  The effect would be greater funding opportunities for the private sector to pursue promising research opportunities.

In addition, the Amendment would strengthen the FDA’s surveillance and enforcement powers for purposes of protecting consumer safety, and put the proper incentives and penalties in place to forestall the introduction of unsafe products to the public.

V. Conclusion

While the 21st Century Cures Act recognizes and addresses a significant issue in the health and welfare of our country, it does not solve the underlying problem causing the lack of significant health-related cures.

Congress could jumpstart private funding for research and development of promising discoveries by adopting the above recommendations in an Amendment to the 21st Century Cures Act.

To minimize concerns for public safety, the approach recommended here could be achieved with an Amendment that would apply only to specific research areas such as Alzheimer’s disease, Parkinson’s disease and/or metastatic cancer where suffering is the greatest and hope is fleeting.

Out of an even further abundance of caution, Congress could implement this Amendment on an optional basis, thereby letting research organizations choose between this approach and the more traditional approach outlined by the Act and the FDA.