Government Reform and Oversight Committee
February 4, 1998 Mr. Charles B. Simone, M.MS., M.D.Charles B. Simone, M.MS., M.D. graduated from Rutgers Medical College (1971-1975). He is an Internist (trained at the Cleveland Clinic 1975-1977), Medical Oncologist (trained at the National Cancer Institute 1977-1982), Tumor Immunologist (trained at the National Cancer Institute 1977-1982), and a Radiation Oncologist (trained at the University of Pennsylvania 1982-1985). Working with Senator Harkin, he helped to shape the Office of Alternative Medicine, National Institutes of Health. In addition, he also helped to organize a Department of Alternative Medicine for Columbia and Mt. Sinai in NYC.
While at the NCI, his basic science research uncovered the fundamental mechanism of how human white blood cells kill, helped show how "complement" proteins aid in killing, demonstrated how adriamycin works, and developed directed effector cells.
One of the first patients he consulted with at the NCI was a senior statesman who was dying of malnutrition secondary to his cancer. Later, a man his own age with a newly pregnant wife came to him at the NCI and asked to be kept alive for the birth of his child. An intensive course of chemotherapy cleaned out the cancer cells, but the patient failed to improve. "I decided at last resort to put him on high doses of vitamins and minerals that quickly produced a temporary recovery.." The man lived to see the birth of his son.
He began devoting some of his time investigating the effects of nutrition on cancer and the possibilities of cancer and disease prevention. The result was Cancer and Nutrition, A Ten Point Plan to Reduce Your Risk of Getting Cancer (1981 McGraw-Hill, revised 1994 Avery). He also wrote Breast Health, Shark Cartilage and Cancer, Prostate Health, KidStart, and Sports and Nutridon.
He has testified as an expert in the fields of cancer, nutrition, nutritional supplementation, disease prevention, and medical care cost reduction before the United States Senate and the United States House of Representatives of 1993, 1994, and 1995.
THE NEED FOR CHANGE
Billions of dollars have been invested in cancer research and treatment since 1971 when President Nixon declared War on Cancer. Each month, it seems, new therapies are trumpeted. Some show promise, most fizzle quickly.
Cancer will emerge as the number one cause of death in the United States by the year 2000. Despite the enormous effort to combat cancer, the number of new cases of nearly every form of cancer has increased annually over the last century. Still worse, from 1930 to the present, despite the introduction of radiation therapy, chemotherapy, and immunotherapy with biological response modifiers, despite CT scans, MR scans, and all the other new medical technology - life spans for almost every form of adult cancer except cervical cancer and lung cancer have remained constant, which means that there has been no significant progress in cancer treatment (Figure 1 attached, data from the National Cancer Institute SEER Program, published by the American Cancer Society each January).
"Cure" is largely elusive or statistically disguised. "Cure" means surviving 5 years after treatment - if death occurs at 5 years and one day, the "cure" is unaltered in the statistical record.
The chilling prospect remains - by the year 2000, two of every five Americans will develop cancer. And most will die.
Because of these dismal survival statistics with existing conventional treatments, we need to redirect our attention to two important areas. Prevention of cancer and other diseases; and pursue totally New Substances or New Modalities that show scientific merit for treatment even though they may not yet be approved by the Food and Drug Administration for widespread use.
FDA REFORM ??
Because FDA funding must be used for more food safety work, it has been estimated that there will be a 60% to 70% reduction in funds that would otherwise be assigned to tenure-track scientists in the Division of Viral Products, Center for Biologics Evaluation and Research (Feinstone SM, Lewis AM, Markoff LJ, Carbone K, Golding H.[all lab chiefs in that Division] Science. January 9, 1998; 279:157-159.
We certainly do not want to lose excellent scientists, however, the dollars earmarked for research should be used only for evaluation of Other governmental agencies are organized for research.
Henry I. Miller, from the Hoover Institution, Stanford University, writes about FDA Reform in the same cited Science article:
First, it calls for "promptly and efficiently reviewing clinical research" "in a timely manner." But these words will not have any impact on the agency's 30 year tradition of risk aversion and foot-dragging.
Second, it calls on FDA to develop a plan by the year 2000 to clear the legendary backlog of products awaiting approval. Congress here makes itself a hostage to an endless series of demands for additional resources the FDA will say it needs to do this.
Third, it codifies many policies that are already in place, giving the impression of a lengthy list of improvements.
The most important provision offers drug companies greater latitude in supplying scientifically sound information to doctors about drugs' "off label" uses (those not yet approved by FDA). Companies are currently prohibited from distributing such critical information. But even this improvement comes at a high price: substantial additional paperwork to convince FDA that formal applications for approval of the new uses are forthcoming. [This provision of "off label" uses is very valuable for the patient. CB Simone, M.D.]
A welcome provision permits manufacturers to submit "health care economics information," such as data on a drug's cost-effectiveness, to hospitals and HMOs.
The bill contains other minor improvements, such as loosened restrictions on health claims for food products and expanded use of third party, including academic institutions, to review medical devices.
However, one provision actually increases the scope of FDA's regulation by expanding its jurisdiction to activities that occur completely within a single state - small-scale research by an academic or a practicing physician testing an innovative therapy.
Many critical reforms recommended by blue-ribbon panels are absent. These include reducing the redundancy of regulation of early-stage clinical trials and a binding reciprocity provision that, for example, would limit the duration of FDA review of a new drug to a maximum of, say 60 days after its approval in the United Kingdom or by the European Medicines Evaluation Agency (thereafter, the FDA would have to show cause why the drug should not be marketed in the United States, or it would automatically be approved).
Following Congress's failure to accomplish significant FDA reform, the costs of drug development (already averaging more than $500 million to bring a single product to market) will continue to rise, fewer drugs will be developed, and market competition will erode. Patients will suffer higher prices and benefit from fewer breakthrough drugs.'
FDA Should Not Be In The Drug Discovery Business
"FDA finds potential cancer treatment" (USA Today 12-12-97)
The Associated Press reported in USA Today on December 12, 1997 that the FDA "found a promising new treatment for cancer and licensed it" to Neopharm Inc. an Illinois biotechnology company. The private firm will need FDA approval to sell it. Obviously, the FDA has a conflict of interest for this approval. The chief executive of Neopharm, William Govier, said "his company may have saved $100 million in dug-development work by merely licensing the FDA's discovery." The FDA Reform Bill passed by Congress includes requirements to speed the review of new vaccines and drugs and to reauthorize the Prescription Drug User Fee Act. To accomplish this, the FDA will tap "user fees" that are charges to companies that submit products for FDA review and approval.
However, the FDA uses about $10 million a year (USA Today article) in industry fees to fund their research labs. The biotechnology industry protested the new drug discovered by the FDA. "It should stick to regulation and leave discovery to industry."
The taxpayer has essentially funded a private company's Research and Development. That company will have saved over $100 million. The taxpayer should be compensated and the FDA should deal only with regulation and not discovery. There are many other Federal research labs that are in the business of discovery.
The Dietary Supplement Health and Education Act of 1994
Having helped to write some of the key language for the Dietary Supplement Health and Education Act of 1994 with Senators Harkin and Hatch, I was very disappointed in the proposed statements of the President's Commission on Dietary Supplement Labels. The Commission issued a draft report for public comment before it made its final recommendations to the President, Congress, and the FDA.
The report was a disaster. It completely ignored the subject Congress created the Commission to address: namely, "how best to provide truthful and non-misleading information to consumers so that such consumers may make informed health care choices." Instead, the Commission simply placed its stamp of approval on the FDA's current prior restraint on all health claims, except those pre-approved and recommended the adoption of safety, reporting, and OTC botanical regulations that are beyond the scope of its delegated authority. The tragedy is compounded by the fact that the Commission's recommendations are required, by law, to be published by FDA as proposed rules, making it possible that the agency will adopt one or more of the suggestions.
Government Interference Pith Choice of Treatment by Informed Patients
I have been called upon many times by patient advocates to determine whether the treatment outcome desired by the patient's guardians or patient will equal or be better than the outcome of existing conventional treatment. Often times, these patients or their guardians find themselves entangled with legal issues because the physician wants to impose the conventional treatment indicating "it will save the patient's life," or "it will cure you." Or, the patient has received all conventional treatment without success and then wants to try an Investigation New Drug approved by the FDA for research purposes. The patient attempts to obtain this drug but finds himself or herself ineligible according to the strict research criteria. In these instances, when a patient has an unwanted treatment unposed upon him or her by a governmental agency, or when he or she desires an Investigational New Drug, I review the medical records to make a determination of the various effective treatment options, and whether any one option is superior to another, and importantly, whether a particular treatment option will increase life span. Remember that a critical measurement in cancer care is whether a specific treatment will increase the life span of the patient. Examples:
You have already heard the eloquent and heart wrenching story of Zachary McConnell by Jonathan Emord, Esq. Zachary, age 5, had a rare brain tumor and was enrolled in a FDA approved Investigational New Drug protocol. While under this treatment the FDA decided to stop the protocol. His parents fought this decision legally.
An eleven year old girl, EU, diagnosed with non-metastatic high-grade osteosarcoma of the left distal femur was treated with three cycles of appropriate chemotherapy with adequate doses for osteosarcoma. Her mother, with whom I spoke, wanted no further chemotherapy and wanted her daughter to proceed to surgery. Her physicians wanted her to have several more months of chemotherapy before the surgery. After reviewing all the data, including the patient's records and imaging scans, I was convinced from the published medical journal articles that the patient should proceed with surgery because no benefit in lifespan or local control is achieved when more than three cycles of chemotherapy is administered before surgery. Any delay in surgery brought a higher risk for distant metastasis. The judge in the case overturned the court order requiring the patient to have more chemotherapy.
TRUE FDA REFORM SHOULD INCLUDE
Easier access to Drugs for terminally ill patients and once a patient is enrolled in an
FDA approved protocol, never stop that treatment. Allow physicians to have access to
"off label" information. Assign New Time Limit for FDA Review of Applications,
and limit FDA review of a new drug to 60 days if that drug has prior approval in United
Kingdom or European Medicines Evaluation Agency. Discontinue FDA 's Discovery Research,
and Recover for the American taxpayer the $100 million saved by Neopharm, Inc., and other
monies possibly gleaned in a similar fashion by other companies. In the short term, hire
additional staff to clear the backlog of products that await approval. Rescind FDA 's
regulatory authority within a single state.
Answers to the Following:
1) How many applications per year are submitted for protocol approval (Investigational New
Drug, New Drug Approval, etc)?
2) How many of these are approved and in what period of time?
3)How many potential applicants stop the process after attempting to complete the
paperwork for the application.
4)How many applications are submitted by "professional" application writers -
attorneys, past FDA people, etc.
5) To how many potential applicants does the hiring of these "professionals"
present an impediment?
6) What is the average cost of getting an application ready for submission to FDA?
7) What is the average length of time needed to complete an application by the applicant?
8)How effective is the FDA at helping potential applicants to complete the application if
an applicant requests help from the FDA?
9) How many patients request from the FDA an "off-label use" treatment or one
that has an IND for which they may not be eligible?
10) How many of those patients receive such treatment?
Informed Consent could be a very powerful tool for the patient. If the concept of Informed Consent was truly enforced and fully explained, patients would then understand the limitations of many treatments. Misinformation is sometimes given to patients. A glaring example is found in a Sunday front page New York Times article on October 26, 1997 entitled 'Vitamin Mania, Millions Take a Gamble on Health.' Larry Norton, M.D., a staff person from Memorial Sloan Kettering, a highly regarded institution, was interviewed and stated:
"Research at his institution showed that large doses of vitamin C could blunt the beneficial effects of chemotherapy for breast cancer. The research showed that breast cancer cells had large numbers of receptors, or docking places, for vitamin C, suggesting that the vitamin acted like a tonic for cancer cells.
And a recent experiment showed that free radicals, chemicals that damage cells in ways that may lead to cancer, are also necessary for some of the mechanism that stop cancer once it gets going. So a substance like vitamin C, in large doses, could have unpredictable effects. It is also known that folio acid can negate the effects of methotrexate, a drug used to treat cancer."
This "information" is absolutely incorrect. Over 200 peer-reviewed scientific articles have been published in medical journals in the 1970s, 1980s, and 1990s. Summarized in books and medical journals, the correct information shows that nutritional modification, including the use of certain nutrients, and proper lifestyle can dramatically decrease the morbidity and side effects of chemotherapy and radiation therapy as well as increase response rates. There have even been some reports that nutritional and lifestyle modification actually increase survival.
Simone, CB. Cancer and Nutrition (1992 revised Avery Publisher).
Simone, CB. Breast Health (1994 Avery Publisher)
Simone CB, Simone NL, Simone CB II. Oncology care augmented with nutritional and lifestyle modification. J Ortho Mol. Med 1997; 12(4): 197-206.
Simone CB, Simone NL, Simone CB II. Folic acid does not interfere with methotrexate. Lancet. 1997; 350: 1556.
Simone CB, Simone NL, Simone CB II. Lifestyle modification in oncology care. In: Prasad, KN ed. Cancer and Nutrition. 1997. Amsterdam, Netherlands, IOS Press.
Simone CB. Nutritional and Lifestyle Modification in Oncology Care. In: Torosian M. Integrated Cancer Management: Surgery, Medical Oncology, and Radiation Oncology. 1998. Marcel Dekkar, New York. (University of Pennsylvania)
Summary
The patient's well being must come first in all instances. Patients need to have access to
treatments and information that potentially may benefit them. The FDA should serve the
public and not be an obstruction.