Overview: Access to Unapproved Investigational Drugs in the U.S.*
Like you, PPMD has had many questions about the way we can access UNAPPROVED investigational therapies in Duchenne. Expanded access, compassionate use, Right to Try – these are all terms we have probably heard, but what do they mean? What are the pros and cons of each? PPMD’s Advocacy team has worked to put together a comprehensive guide to help answer your questions and clarify some of the confusion around these complex pathways to unapproved therapies.
Jump to:
- Definition
- How it works
- Who is eligible
- Coverage, Cost, and Reimbursement for an Investigational Drug
- Coverage, Cost, and Reimbursement of Routine Costs
- Monitoring Outcomes
- Liability
- Informed Consent
- Role of the Physician
*This chart does not cover off-label/investigational uses of approved drugs.
Definition
**State laws, regulations, and guidances potentially include additional elements
How it works
**State laws, regulations, and guidances potentially include additional elements
Who is eligible
**State laws, regulations, and guidances potentially include additional elements
Coverage, Cost, and Reimbursement for an Investigational Drug
Participation in Clinical Trials | FDA: Expanded Access for Individual Patients (includes an option for emergency use) | FDA: Expanded Access for Intermediate-Size Patient Populations | FDA: Expanded Access for Widespread Treatment Use | Federal Right To Try Legislation ("RTT")** |
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A manufacturer may charge eligible patients for direct costs of the drug (only) if they meet certain criteria outlined in 21 C.F.R. 312.8. Many manufacturers do not charge patients the direct costs because they wish to withhold proprietary cost information or for other reasons. Additionally, third party payers (including private insurers and Medicare) are not required to provide coverage for any of the direct costs charged by the manufacturer. Payers generally do not require an investigational drug itself unless otherwise covered outside of the clinical trial. | The manufacturer may require eligible patients to pay the costs associated with manufacturing the drug; however they must obtain authorization from the FDA. There are no federal requirements for insurance companies to cover an experimental drug. 21 C.F.R. § 312.8(c) and (d) | The manufacturer may require eligible patients to pay the costs associated with the manufacturing the drug; however they must obtain authorization from the FDA. There are no federal requirements for insurance companies to cover an experimental drug. 21 C.F.R. § 312.8(c) and (d) | The manufacturer may require eligible patients to pay the costs associated with the manufacturing the drug; however they must obtain authorization from the FDA. There are no federal requirements for insurance companies to cover an experimental drug. 21 C.F.R. § 312.8(c) and (d) | The manufacturer may require eligible patients to pay specific costs associated with manufacturing the drug. They are not required to obtain authorization from FDA to do so. |
Coverage, Cost, and Reimbursement of Routine Costs
Participation in Clinical Trials | FDA: Expanded Access for Individual Patients (includes an option for emergency use) | FDA: Expanded Access for Intermediate-Size Patient Populations | FDA: Expanded Access for Widespread Treatment Use | Federal Right To Try Legislation ("RTT")** |
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Routine costs of a clinical trial that are otherwise covered by the third party payer may be covered. There are different rules that apply to coverage for routine care in clinical trials for Medicare, Medicaid, and private payers. Manufacturers sometimes pay for routine costs provided to an indigent uninsured patient. | Routine costs for INDs under expanded access are likely treated similarly as broader clinical trials and may be covered by the third party payer, unless upon medical management review, the payer finds that the use no longer meets qualifying criteria or jeopardizes the safety or welfare of the enrollee. Different rules apply for Medicare, Medicaid, and private payers. | Routine costs for INDs under expanded access are likely treated similarly as broader clinical trials and may be covered by the third party payer, unless upon medical management review, the payer finds that the use no longer meets qualifying criteria or jeopardizes the safety or welfare of the enrollee. Different rules apply for Medicare, Medicaid, and private payers. | Routine costs for INDs under expanded access are likely treated similarly as broader clinical trials and may be covered by the third party payer, unless upon medical management review, the payer finds that the use no longer meets qualifying criteria or jeopardizes the safety or welfare of the enrollee. Different rules apply for Medicare, Medicaid, and private payers. | Routine costs of a clinical trial that are otherwise covered by the third party payer may be covered (similar to expanded access). Coverage of routine costs may be withdrawn if, upon medical management review, the payer finds that the use no longer meets qualifying criteria or jeopardizes the safety or welfare of the enrollee. Different rules apply for Medicare, Medicaid, and private payers. |
Monitoring Outcomes
Participation in Clinical Trials | FDA: Expanded Access for Individual Patients (includes an option for emergency use) | FDA: Expanded Access for Intermediate-Size Patient Populations | FDA: Expanded Access for Widespread Treatment Use | Federal Right To Try Legislation ("RTT")** |
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The IND will contain extensive reporting obligations that the manufacturer/study sponsor must make to the FDA. Ethically, all major regulators place gaining dispositive data over any individual patient’s needs, in hopes that the data gained could help more patients in the future. Therefore, regulators such as the FDA would prefer that patients, if eligible, enroll in a clinical trial, rather than accessing drugs through Expanded Access or RTT mechanisms. | The sponsor (manufacturer or physician) of the relevant IND (either the existing IND under which there is a Single Patient Protocol or the Expanded Access IND) must report all adverse events to the FDA and undertake all other reporting required by the IND. | The sponsor (manufacturer or physician) of the relevant IND (either the existing IND under which there is an Intermediate-Size Patient Protocol or the Expanded Access IND) must report all adverse events to the FDA, and undertake all other reporting required by the IND. | The sponsor (manufacturer or physician) of the relevant IND (either the existing IND under which there is a Treatment Protocol or a Treatment IND) must report all adverse events to the FDA, and undertake all other reporting required by the IND. | RTT provides that “[t]he manufacturer or sponsor of an eligible investigational drug shall submit to the [HHS] Secretary an annual summary of any use of such drug under [RTT]” that includes "the number of doses supplied, the number of patients treated, the uses for which the drug was made available, and any known serious adverse events.” Finally, the Secretary of HHS must post an annual summary report of the use of RTT on the FDA website. Thus, manufacturers will require that physicians provide this information to them. |
Liability
**State laws, regulations, and guidances potentially include additional elements
Informed Consent
Participation in Clinical Trials | FDA: Expanded Access for Individual Patients (includes an option for emergency use) | FDA: Expanded Access for Intermediate-Size Patient Populations | FDA: Expanded Access for Widespread Treatment Use | Federal Right To Try Legislation ("RTT")** |
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Patients must provide informed consent prior to initiating treatment of an experimental drug. | Patients must provide informed consent prior to initiating treatment of an experimental drug. FDA website: "Am I protected from risks?" | Patients must provide informed consent prior to initiating treatment of an experimental drug. FDA website: "Am I protected from risks?" | Patients must provide informed consent prior to initiating treatment of an experimental drug. FDA website: "Am I protected from risks?" | A patient must provide informed consent prior to initiating treatment of the investigational drug; however RTT specifically exempts participation from being covered by IRB regulations. |
Role of the Physician
Participation in Clinical Trials | FDA: Expanded Access for Individual Patients (includes an option for emergency use) | FDA: Expanded Access for Intermediate-Size Patient Populations | FDA: Expanded Access for Widespread Treatment Use | Federal Right To Try Legislation ("RTT")** |
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The physician is in the role of investigator for the clinical trial. The physician may be the patient's usual, treating physician, who happens to be working on the clinical trial, or the patient may see the investigating physician only for study related treatment, and continue seeing their original doctor for everything else. | Physician is in the role of clinician treating a specific patient. | Physician is in the role of clinician. | Physician is in the role of clinician. | Physician is in the role of clinician. |