Single Patients

Single Patients2018-08-13T18:12:25+00:00

Single Patients

Clinical Research Pathways works with IRBs and physicians to make it easier for single patients to navigate the expanded access process. As a resource on expanded access, we also have developed “Points for Patients to Consider” to help critically ill patients understand the options available once standard treatment choices have been exhausted. We encourage patient advocacy groups to share this document in either PDF or brochure form. 

In addition, we provide helpful information on Making Sense of the New Right-to-Try Law.


For IRBs

When reviewing drugs for expanded access, IRBs face four challenges:

  • To speed up the review process for patients who truly are almost out of time.
  • To ensure that the experimental medicine will not cause undue harm to the patients involved.
  • To ensure that patients make informed decisions about using the experimental medicine.
  • To avoid jeopardizing drug approval for future.

Clinical Research Pathways has identified the following four-step process to support IRBs and desperately ill patients. A PDF version can be downloaded here.

Streamlining Procedures for Single Patient Expanded Access Requests Involving Investigational New Drugs

Revise IRB application procedures so that the treating physician may submit as the application:

  • FDA Form 3926
  • Investigator brochure or another source describing risks and potential benefits of the treatment
  • Draft consent document
Revise procedures to ensure that your IRB is able to handle requests in a timely fashion.

  • As of October 3, 2017, FDA permits the IRB chair or designee to review and concur with the expanded access request.
Provide recommendations or similar guidance to your IRB members about how to review single patient expanded access requests.

  • Confirm the medical evaluation of the patient’s condition based on the information provided by the treating physician. This individual must be able to confirm or deny the claim that there is no comparable or satisfactory alternative available.
  • Ensure that informed consent or appropriate permissions will be obtained and documented. Given the compassionate nature of the request and FDA’s involvement, consent documents should meet the requirements listed in 21 CFR 50.25, using plain language that is specifically aimed at “patients” who expect direct benefit, as opposed to “subjects” who may not expect benefit.
  • Receive documentation that FDA has made its determinations regarding safety and effectiveness and has given clearance for the use.  Request the IND number and any documentation from FDA.
  • Review the physician’s treatment plan (or sponsor-provided treatment protocol) and determine that it makes adequate provision for ensuring the safety of the patient including adequate monitoring (timing and type of tests/exams, etc.) and appropriate plans for collecting and reporting the data.
Publish procedures so that they are available to treating physicians and IRB members.

 

Assistance with IRB Procedures

We encourage all IRBs to streamline the review process so that every patient request for expanded access is approved quickly. For more information, including assistance with your IRB procedures, please contact Clinical Research Pathways at info@clinicalresearchpathways.org or call 404.386.8982. Together, we can make a difficult time a little easier for desperately ill patients and their families.

 

For Physicians

The treating physician is the link between desperately ill patients and three key players in the expanded access process: the drug manufacturer, the Food and Drug Administration (FDA), and the institutional review board (IRB). Once approval is obtained, the physician also administers the experimental medicine and monitors the patient’s response.

Because many physicians are not familiar with the process and their responsibilities, Clinical Research Pathways has summed them up below and in a PDF. We’ve also provided step-by-step instructions to assist you.

Responsibilities of a Sponsor-Investigator (Treating Physician):

  • Apply to and obtain approval from FDA and an IRB prior to administering the investigational product.
  • Seek IRB approval for continuing review if the treatment use extends longer than one year or a second dose is needed.
  • Obtain and document appropriate informed consent from the patient or legally authorized representative prior to treatment.
  • Maintain accurate case history records and observations related to provision of product, including adverse events.
  • Report adverse events as required by FDA.
  • Maintain accurate documentation of the disposition of investigational product, including dates, quantity, and use.
  • Adhere to reporting obligations of IRB, FDA, and sponsor.
  • Prepare and send summary report of treatment use to sponsor and FDA.
  • Maintain confidentiality of the information both about the patient and the condition.
  • Comply with applicable local laws and institutional policies.

 

Step-by-Step Process to Obtain a Single Patient IND (Non-emergency)

A PDF version of this document is available here.

  1. Discuss available treatment options with the patient and decide, along with your patient, whether a clinical trial or treating with an investigational drug, biologic, or device outside a clinical trial is appropriate. This will be dependent upon the patient’s medical history, whether there are approved therapies available with which the patient has not been treated, and whether they are eligible to enter a clinical trial for the product. Only patients with a serious or life-threatening disease or condition are eligible for expanded access consideration.
  2. Select the investigational product that you want to use for treatment. This may occur in several ways: the patient brings information about the investigational product to you, you consult clinicaltrials.gov or RUF Navigator to find which investigational products are available through a company’s expanded access program, you contact the drug, biologic or device company.Every company is mandated by the 21st Century Cures Act to publish its policy regarding expanded access, and provide contact information for requests.A company that does not have a listed expanded access program may be willing to provide its product outside of its ongoing clinical trial(s) and, therefore, you should contact the company.
  3. Follow the company’s instructions for requesting a single patient IND (treatment use).
  4. After you receive the company’s decision, if the company agrees to provide the product, they will provide a Letter of Authorization (LOA), allowing FDA to cross-reference their Investigational New Drug Application (IND). This signals FDA that the company will make their product available outside of the clinical trial setting.See FDA’s Expanded Access Contact Information website for physicians to locate the appropriate review division to file the request. You will need to complete FDA Form 3926 (you may need to open the page in Internet Explorer or save the document as a PDF to your desktop by selecting “save page as” under your browser’s file menu before opening it) describing the patient’s medical history and current status, proposed treatment protocol (such as dose, treatment duration, concomitant conditions/medications, etc., and rationale for the proposed treatment). You will also need to attach your curriculum vitae to confirm medical qualification, and provide any background information about the product, regarding known safety or efficacy, and the letter of authorization (LOA) from the company. You will also confirm on the application that treatment will not begin without prospective IRB review and documentation of informed consent, once you receive confirmation from FDA.
  5. FDA has up to 30 days to make a determination, and usually will respond sooner. If the determination is to proceed, FDA will send you a letter with the IND number and any concerns, recommendations, or stipulations.
  6. While you are waiting for FDA’s determination, contact the IRB office in your institution or the IRB that your institution uses to make them aware that the expanded access request will be coming to them shortly for review. If you don’t have access to an IRB, contact Clinical Research Pathways at info@clinicalresearchpathways.org or call 404.386.8982 to find an IRB that will conduct the review for you.After you receive FDA approval, submit Form 3926, a draft informed consent document, and any other documents required by the IRB for review. Be sure to check the box on Form 3926 requesting a waiver of the requirement for the full IRB to review the request. The IRB chair or a designee will review the request.
  7. Once you have received IRB approval, and the patient has reviewed and signed the informed consent document, you may begin to treat the patient.
  8. Review FDA’s requirements for physicians who treat patients under a single patient IND (above).

 

Finding an IRB

Please contact Clinical Research Pathways at info@clinicalresearchpathways.org or call 404.386.8982 if you need assistance finding an IRB to review an expanded access request.

Points for Patients to Consider

If you or a loved one is critically ill and has exhausted standard treatment options, you face some difficult choices. To help you make informed decisions, Clinical Research Pathways has developed educational materials on clinical trials and the process for requesting expanded access to experimental medicines. 

The information is available as a PDF and brochure to make it easy for patient advocacy groups to print and distribute it. 

Making Sense of the New Right-to-Try Law

A PDF version of this document is available here

On May 29, President Trump signed a federal right-to-try law known as the “Trickett Wendler, Frank Mongiello, Jordan McLinn, and Matthew Bellina Right to Try Act of 2017 S.204.” The new law amends the Food, Drug, and Cosmetics Act to create a second pathway for certain patients to access investigational drugs outside a clinical trial. This new pathway will co-exist with FDA’s existing expanded access program.

While it is too soon to know exactly how this new access route will work, a few things are clear:

  • The new law applies only to investigational drugs. It does not apply to medical devices.
  • It applies to individual or single patient treatment uses. It does not apply to intermediate-size patient populations or treatment-wide expanded access (treatment uses). These types of expanded access continue to follow FDA requirements under FDA’s expanded access program.
  • It applies to investigational drugs that:
    • Have completed a Phase 1 clinical trial (defined under 21 CFR 312.21).
    • Have not been approved or licensed by FDA.
    • Are being actively studied in a clinical trial or are included in an application for approval has been filed with FDA.
  • It applies only to certain types of patients:
    1. Patients who have been diagnosed with a life-threatening disease or condition. Life-threatening is defined in FDA regulation (21 CFR 312.81) as:
      • Diseases or conditions where the likelihood of death is high unless the course of the disease is interrupted; and
      • Diseases or conditions with potentially fatal outcomes, where the end point of clinical trial analysis is survival.
    2. Patients who have exhausted approved treatment options and are unable to participate in a clinical trial involving an eligible investigational drug (defined above)
      In addition:

      • A physician who is in good standing with the physician’s licensing organization or board and will not be compensated directly by the manufacturer must certify that the two conditions are met.
      • Patients or a legally authorized representative of the patient must provide to the physician written informed consent regarding the eligible investigational drug.

  • The new law does not require a sponsor/manufacturer, prescriber, dispenser, or other individual entity to provide access to an eligible investigational drug. Sponsors retain their right to deny requests.
  • The new law exempts physicians or manufacturers who provide eligible investigational drugs to eligible patients from seeking FDA approval and receiving an IND, and from the requirement for institutional review board (IRB) review and approval.
  • The new law exempts a sponsor or manufacturer, prescriber, dispenser, or other individual entity from liability, unless the relevant conduct constitutes reckless or willful misconduct, gross negligence, or an intentional tort under any applicable state law.
  • FDA may not use the clinical outcomes associated with these treatment uses to delay or adversely affect the review or approval of the investigational drug unless:
    • FDA determines that the use of the clinical outcome is critical to determining the safety of the investigational drug or the sponsor requests use of the clinical outcome.
  • The drug manufacturer or sponsor must submit to FDA an annual summary of any use of an investigational drug under this new right-to-try law.

It is unknown at this point exactly how this new law will be implemented, whether a revision to the code of federal regulations will be required so that FDA may implement the new law, and whether this federal law will preempt state right-to-try laws.

Drug manufacturers and institutions with whom physicians are affiliated can decide to continue to provide expanded access under the existing FDA program. Nothing in the new law prohibits an entity from filing an IND for a single patient expanded access treatment use, or from seeking IRB approval to ensure that a patient’s interests are appropriately respected and protected, regardless of whether access is provided under an IND.

The complete text of Senate Bill 204 can be found here.

 

Important documents