State Cancer Legislative Database Program State Laws Concerning Clinical Trials and Off-Label Drug Use for Cancer Patients Kristianna G. Pettibone, M.S.1 Raedell Wallace 1 Randi Field, J.D. 1 Regina el Arculi, M.A. 2 Presented at the American Public Health Association's 130th Annual Meeting and Exposition Philadelphia, PA November 11, 2002 1 The MayaTech Corporation 2 National Cancer Institute

Introduction Objective: To review state level insurance mandates for coverage of participation in clinical trials and off-label drug use. Methodology: Data from the National Cancer Institute’s State Cancer Legislative Database (SCLD) were analyzed to determine the scope and content of state legislation addressing coverage of clinical trials and off-label drug use. State-level laws enacted by June 30, 2002 were analyzed.

Background Clinical Trials According to the National Institutes of Health, a clinical trial is a research study to determine the safety and effectiveness of new drugs and therapies or to determine new ways to use existing treatments. Our research will focus on cancer treatment trials which are designed to test new treatments, new combinations of drugs, or new approaches to surgery or radiation therapy. In 1994, Rhode Island was the first state to enact a law requiring coverage of costs associated with participating in a clinical trial.

Background (continued) Off-Label Drug Use According to the National Cancer Institute, off-label drug use refers to the use of an approved drug for any purpose, or in any manner, other than what is described in the drug’s labeling. A 1991 study by the U.S. General Accounting Office found that one-third of all drug administrations to cancer patients are off-label and more than half of cancer patients received at least one drug for an off-label indication. In 1989, Michigan was the first state to enact a law requiring coverage of off-label prescription drug use.

Phases of Clinical Trials (NIH, 2002) Phase I: Study testing a new drug/treatment for the first time in a small group (20-80 people) to determine safety, safe dosage range, and side effects. Phase II: Study expanded to a larger group (100-300 people) to evaluate effectiveness and safety. Phase III: Study further expanded to large groups (1000-3000 people) to confirm effectiveness, monitor side effects, compare it to common treatments, and collect information to enable safe use of drug/treatment. Phase IV: Post-marketing studies conducted to gather additional information including drug risks, benefits, and optimal use.

States with Mandates for Coverage of Clinical Trials and Type of Insurer Addressed All states with laws addressing coverage of clinical trials require insurers to provide coverage of clinical trials. The type of insurer addressed by the law varies by state. Individual and group insurers required to provide coverage. Managed care and individual and group insurers required to provide coverage.

Clinical Trial Phases Covered Coverage of certain phases of clinical trials varies by state. Number of States AZ CA CT GA IL LA MD NH NM RI VA AZ CA GA IL LA MD NH NM RI VA AZ CA IL LA MD NH NM RI VA AZ CA MD NH VA New Hampshire (Phase I and II) and Virginia (Phase I) require that coverage for certain clinical trials be decided on a case-by-case basis. These states are included in the counts above.

Organizations Approved to Conduct Clinical Trials Each state requires that clinical trials be conducted by specified organizations in order to qualify for coverage. Number of States AZ CA CT GA IL LA MD NH NM RI VA AZ CA CT LA MD NH NM RI VA AZ CA CT IL LA NH NM RI CT GA MD RI VA AZ CA CT LA NM AZ FDA: Food and Drug Administration NIH: National Institutes of Health NCI: National Cancer Institute DOD: Department of Defense VA: Department of Veterans Affairs

Specific Conditions of Clinical Trial Coverage The laws in eight states explicitly require that certain conditions be met before coverage for clinical trials is provided. Personnel providing treatment are doing so within their scope of practice, experience, and training AND no clearly superior, non-investigational treatment exists AND data provide a reasonable expectation that the treatment will be at least as efficacious as a non-investigational treatment. Data provide a reasonable expectation that the treatment will be at least as efficacious as a non-investigational treatment No clearly superior, non-investigational treatment exists AND data provide a reasonable expectation that the treatment will be at least as efficacious as a non-investigational treatment. Institutional Review Board (IRB) approval is required.

Miscellaneous Notes on Mandated Coverage of Clinical Trials Rhode Island’s law is the only one that does not specifically require coverage of routine patient care costs, which typically include any costs or services usually covered by the policy. Reimbursement must be considered payment in full in Arizona and New Mexico. Georgia only requires coverage of clinical trials for dependent children. Vermont was not included in these data. The state has in place requirements similar to those addressed here, but has implemented them through regulation rather than legislation.

States with Mandates for Coverage of Off-Label Drug Use Twenty-six states have laws addressing cancer-specific off-label drug use. Individual and group insurers and managed care insurers are required to provide coverage, if they provide coverage for prescription drugs in general. Individual and group insurers and managed care insurers are required to provide coverage. Coverage is not contingent on the insurer providing coverage for prescription drugs in general. Individual and group insurers are required to provide coverage, if they provide coverage for prescription drugs in general.

Authorities That Must Recognize or Recommend the Off-Label Treatment USPDI: U.S. Pharmacopeia Drug Information AMADE: American Medical Association Drug Evaluation AHFSDI: American Hospital Formulary Service Drug Information DRUGDEX: Private drug evaluation listing Number of States Michigan, New Hampshire, and Oklahoma do not specify inclusion of a drug in a reference compendium as a condition of coverage.

Medically Necessary Services Seventeen states require that insurers also provide coverage of any related, medically necessary services. Medically necessary services covered. Medically necessary services not covered.

Experimental or Contraindicated Drugs Not Covered Twenty states do not require coverage of experimental and/or contraindicated drugs. Three states do not require coverage of contraindicated drugs. Three states have no restrictions Experimental and/or contraindicated drugs not covered. Contraindicated drugs not covered. No restrictions.

Deductibles, Copayments, or Coinsurance Requirements for Off-Label Drug Use and Clinical Trials Eleven states have laws that indicate that cost-sharing may apply to coverage of off-label drug use or clinical trials. Cost-sharing is not addressed in the legislation of the other states. Deductibles, copays, or coinsurance requirements for off-label drug use may apply. Deductibles, copays, or coinsurance requirements for clinical trials may apply. Deductibles, copays, or coinsurance requirements for both off-label drug use and clinical trials may apply. Although Georgia’s law does not distinguish among deductibles, copayments, or coinsurance, the state has been included here, because its law states that general “cost-sharing arrangements” may apply.

Enforcement and Review Four states—Arizona, Georgia, Louisiana, and New Mexico—that mandate coverage of clinical trials and seven states—Alabama, Georgia, Illinois, Indiana, Kansas, Kentucky, and Minnesota—that mandate coverage of off-label drug use indicate that a State Commissioner of Insurance (or similar entity) is responsible for enforcement of these provisions.

Miscellaneous Notes on Mandated Coverage of Off-Label Drug Use Eight states—California, Colorado, Maryland, Nevada, New Jersey, North Dakota, Oregon, and Tennessee—have enacted off-label drug use laws that do not explicitly address cancer treatment; instead they refer to life-threatening conditions or generic off-label indications. Because they are not cancer-specific, they fall outside the scope of the SCLD Program and are not included in this analysis. Ohio has off-label drug use laws that address both cancer-specific use and generic use.