Reprinted Articles

Secretary's Advisory Committee on Regulatory Reform

January 11, 2002

Douglas L. Wood, M.D., Chairman
Regulatory Reform Initiative
Office of the Assistant Secretary for Planning and Evaluation
200 Independence Avenue, SW
Washington, DC 20201

Attention: Christy Schmidt, Executive Coordinator

Regarding: Secretary's Advisory Committee on Regulatory Reform; Request for Public Input, FR Doc. 02-239, Vol. 67, No. 3, January 4, 2002.

Dear Dr. Wood:

The National Organization for Rare Disorders (NORD) welcomes the opportunity to submit comments regarding the Secretary's Advisory Committee on Regulatory Reform. We will be confining our comments to two areas: (1) Biomedical and health services research, including Protection of Human Subjects in Research and, (2) Coverage of rare diseases through Medicare and other Social Security entitlement programs.

Background

NORD is a federation of approximately 125 voluntary health organizations and over 70,000 individual patients, healthcare providers and clinical researchers dedicated to helping people with rare "orphan" diseases. We are dedicated to helping people with rare "orphan' diseases and assisting the organizations that serve them. Our commitment to the estimated 25 million Americans suffering with approximately 6,000 known rare disorders is the identification, treatment and cure of rare disorders through programs of education, advocacy, research, and service.

An orphan disease is defined by statute as any disease or condition impacting less than 200,000 Americans. It makes no difference whether you are male or female, rich or poor, young or old, white, African-American, Latino, Asian or American Indian. These diseases affect everyone.

Rare "orphan" diseases include such better known diseases as Sickle Cell anemia, Tay-Sachs disease, Hemophilia, Fanconi's anemia, Tourette Syndrome, Lou Gehrig's disease, scleroderma, etc. It also includes obscure diseases such as Landau Kleffner Syndrome, Wilson's disease, mastocytosis, Canavan disease, and fibrodysplasia osssificans progressiva (FOP).

Because little research is being pursued for most of the rare diseases, millions are being left behind simply because they lack the tools and resources available to many prevalent disease patients that enable them to exploit the vast resources of the National Institutes of Health (NIH) and the Food and Drug Administration (FDA). In fact, the National Commission on Orphan Diseases found overwhelming

evidence of rare disease patients' difficulty in obtaining a timely and accurate diagnosis, and information about their rare disease, because physicians are often unfamiliar with the often vague and confusing symptoms. Almost one-third of the patients receive a rare disease diagnosis one to five years after the onset of symptoms. One in seven go undiagnosed for six years or more.

These findings were later reaffirmed in the January 2001 report of the Special Emphasis Panel of the National Institutes of Health on the Coordination of Rare Diseases Research when the panel discovered that "resources and support for basic, translational and clinical research of rare diseases and conditions are inadequate." The report also found that "research related to rare diseases requires patient participation, if not as participants in clinical trials then as donors of blood or tissue samples."

BIOMEDICAL RESEARCH: Protection of Human Subjects

Unfortunately, many people today, including those outside the rare disease community, are fearful or unwilling to participate in desperately needed clinical research. One has only to read the headlines to understand why -

• Death Heightens Scrutiny of Clinical Tests, Concerns About Volunteers' Safety has Prompted Calls for New Rules, Expanded Protections, Washington Post, June 25, 2001 - "…a number of serious incidents have shown continuing weaknesses in the system. Concerns about patient safety stopped clinical trials at university medical schools in Oklahoma, Alabama, North Carolina and Massachusetts."
  
  
• Dying for Science, A Crackdown on Risky Human Experiments, Newsweek, July 30, 2001 - "Two years ago the inspector general of the Department of Health and Human Services warned that the system safeguarding human subjects is in danger of a meltdown. The boards that review proposed studies are overburdened, understaffed and shot through with conflicts of interest."
  
  
• EPA Used Data from Human Pesticide Tests, Washington Post, November 29, 2001 - "Unlike trials of medicine, human pesticide trials carry the ethical problem that volunteers have no prospect of receiving any medical benefit from them. Ethicists charge that the paid trials mostly draw poor people, whose circumstances coerce them into participation."
  

Although this Committee has been charged with the task of reviewing and making recommendations to reduce "unnecessary, excessive, or inappropriate" regulatory burdens in healthcare in order to "respond faster to the concerns of patients, health care providers, state and local governments, other institutions, and other individual Americans who are affected by HHS rules," NORD recommends that this Committee strengthen and enhance current regulations to address the inconsistency of human research protections (see examples above). During your deliberations, we also ask that this Committee consider the findings of the National Bioethics Advisory Commission (NBAC) to ensure the ethical protections of human research subjects in both the public and private sectors as follows :

NBAC Recommendation 2.1

The federal oversight system should protect the rights and welfare of human research participants by requiring 1) independent review of risks and potential benefits, and 2) voluntary informed consent. Protection should be available to participants in both publicly and privately sponsored research. Federal legislation should be enacted to provide such protection.

NBAC Recommendation 2.2

To ensure the protection of the rights and welfare of all research participants, federal legislation should be enacted to create a single, independent federal office, the National Office for Human Research Oversight (NOHRO), to lead and coordinate the oversight system. This office should be responsible for policy development, regulatory reform, research review and monitoring, research ethics education, and enforcement.

Note: Currently, 18 federal agencies are signatories to the Common Rule, but at least 69 other federal departments, including the FDA, responsible for conducting or supporting human research programs are not. Volunteers in privately funded clinical trials do not have protections equal to those in publicly funded research trials.

Rather than establish yet another office, the current HHS Office of Human Research Protections (OHRP) should be given sufficient resources and authority to oversee human research protections to protect the welfare of participants in all publicly AND privately funded human research in the United States. There should be a single set of human protection rules that all researchers must comply with. Non-medical research (e.g., social, anthropological and behavioral research) should be reviewed by non-medical experts on local Institutional Review Boards (IRBs). Composition of IRBs should be broadened to include a minimum of one-third who represent patients and the general public, and who are not employees of the institution.

NBAC Recommendation 2.3

A unified, comprehensive federal policy embodied in a single set of regulations and guidance should be created that would apply to all types of research involving human participants.

BIOMEDICAL RESEARCH: Conflicts of Interest

At the request of Senator Bill Frist, Ranking Minority Member of the Subcommittee on Public Health, Committee on Health, Education, Labor and Pensions, the Government Accounting Office (GAO) recently conducted a study regarding "allegations that conflicts of interest may have affected the integrity of biomedical research and led to harming human research subjects."

This disturbing report found that "…financial conflicts of interest may affect the recruitment of human research subjects such that inappropriate participants are enrolled. These conflicts also may influence the informed consent process - by which the risks and benefits of a study are communicated to the participants - resulting in participants who are not fully informed about a study's potential harm to them."

The GAO recommends that HHS "undertake efforts to highlight and communicate best practices for institutions to identify and manage investigator and institutional financial conflicts of interest." It was also recommended that HHS "develop specific guidance or regulations to address institutional financial conflicts of interest." Here again, the critically important role of FDA falls short; FDA requires that sponsors submit conflict-of-interest data to the agency after the research is completed.

NORD concurs with the GAO's recommendations and we respectfully request that this Committee incorporate them into your final report to the Secretary. Each abuse of the human subject protection system threatens the very foundation of scientific research and development of new treatments and cures. If patients do not trust the system, they will not volunteer to participate, and the loss of public trust has been profound in recent years.

MEDICARE AND MEDICAID COVERAGE

NORD would also like to comment on HHS regulations related to Social Security, Medicare, and Medicaid that impose an unnecessary or unreasonable burden on the rare disease community.

Most government entitlement programs such as Medicare, Medicaid and Social Security Disability address common health problems and classify them into broad disease categories. For instance, Medicare uses the Diagnostic Related Groups (DRG) classification system for hospital services. Social Security publishes a Listing of Impairments that groups diseases and conditions into narrowly defined categories. Unfortunately for the rare disease community, most patients do not fit neatly into these categories because the very nature of their disorder is unusual.

Consequently, the burden of proof lies not on the system, but on the patient who not only suffers the indignities of sometimes waiting years to reach a diagnosis, causing untold emotional, physical and financial strain, but also is forced to wait extended periods to receive desperately needed medical care while appealing negative disability decisions.

For instance, we are reminded of a woman with Myasthenia Gravis who was denied Social Security Disability benefits because, even though she had to hold her eyelids open with her hands, she was not blind and SSDI said she could therefore work. Similarly, if a rare disease patient covered by Medicare is admitted to the hospital for treatment of their disease, hospitals more often than not must merge that patient into the "other" category. Patients then may receive substandard or delayed care because healthcare providers fear the claim may be questioned and/or reimbursement delayed because there is no clear DRG for that diagnosis.

Some of the same problems exist in the state-run Medicaid programs, and vary widely from state to state. For example, in order to control costs, many Medicaid programs limit prescriptions to three or five per month. But many seriously ill rare disease patients must take many more than three to five drugs each month just to stay alive.

Although NORD does not have specific recommendations to address the many problems experienced by rare disease patients in specific entitlement programs, a system must be established to address the healthcare needs of those who fall outside the norm. We would suggest that these classification groups - such as DRG's and SSDI's Listing of Impairments - should not be based on diagnoses, but rather on symptoms. If one loses 50 percent use of an arm, for example, it should not matter whether the cause is a stroke, or accident, or a rare paralyzing disorder such as Moersch-Woltmann Syndrome (Stiff-Man Syndrome), or a rare bone disorder that limits mobility.

CONCLUSION

For decades committees and commissions have studied the problems related to biomedical research. It is now time to revamp the patchwork oversight system and enact federal regulations that will ensure the explicit rights of all research volunteers. The disparate rules and regulations of ALL agencies conducting research in existence today are inadequate, leaving too much room for local institutions to misinterpret the rules. Since the death of Jesse Gelsinger at the University of Pennsylvania, and Ellen Roche at Johns Hopkins, patients nationwide are refusing to participate as human research subjects. Confusion must be eliminated and public trust restored if clinical research is to continue at its current pace.

Today, too many scientists, clinical researchers and universities see the human protection system simply as a logjam of red tape, and IRBs have become liability protection watchdogs for the institutions themselves. They see human protection oversight as a barrier to research, not a safeguard. The system must, "First do no harm." In the 21st century it is incredible that a study like the one recently uncovered at Johns Hopkins would be approved by an IRB knowing full well that at least some healthy children would be unnecessarily exposed to dangerous levels of lead, leading to permanent brain damage. In short, Mr. Secretary, we believe that many government regulations for health programs should be stronger, not weaker, and indeed weakening protective regulations will further erode public trust in NIH, FDA, and DHHS.

NORD looks forward to the opportunity to work with the Secretary's Advisory Committee on Regulatory Reform as it relates to the rare disease community. For additional information, please contact Diane E. Dorman, Vice President for Public Policy, at: ddorman@rarediseases.org or at (202) 496-1296.

Thank you for this opportunity to provide our thoughts and insights on regulatory reform.

Sincerely,

Abbey S. Meyers
President

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