You should work with your child’s doctor when initiating a request for a compassionate use drug because the doctor will be submitting the needed paperwork. The first and most important step is to obtain agreement from the drug company to supply the drug for your child. If the company agrees to provide the unapproved drug, you and your doctor will need to receive approvals from the U.S. Food and Drug Administration (FDA) and a hospital Institutional Review Board (IRB).
1. Identifying a drug for which you might request a compassionate use access
To obtain access to a not-yet-approved medicine for your child, you will need to ask your child’s doctor to apply for compassionate use.
Important issues to discuss with your doctor before initiating the compassionate use application include benefits and risks. Compassionate use is for medicines that are unapproved because they have not yet been proven to be safe or effective. Does the preliminary research show that the drug might work? What are the known risks of the drug? Are there potential risks for children that have not been identified in adult patients? Some risks may be unknown.
Your doctor might have reasons to think that an unapproved drug is too risky, will not be helpful for your child’s condition, or he or she may not be willing to manage the use of an investigational drug. You can ask another doctor for a second opinion, or contact your child’s disease advocacy group.
2. Requesting compassionate use access to a drug from a company
Usually the most challenging step is to obtain the drug from the pharmaceutical or biotech company developing the drug. It is entirely within a company’s discretion as to whether it approves a compassionate use request. There is no legal timeline requirement for the response.
The first step is to identify the point of contact in a company to whom your physician will send the compassionate use request and who is responsible for the company’s response. Kids v Cancer can assist you and your physician in identifying the point of contact in a company.
The next step is for your physician to contact a company requesting compassionate use access to the drug. We provide the template letter and can assist your physician in understanding the criteria that the company may consider when reviewing the application. We can also assist your physician by reviewing the request before it is sent.
If a company agrees to provide the drug on a compassionate use basis, it will send your physician a Letter of Authorization (LOA, example here). This letter is a part of a package that your doctor will need to submit to the FDA. In an emergency, FDA will consider requests without a LOA, but it needs to be provided within 15 working days of FDA’s authorization.
The company may not have enough of the drug available for all patients requesting compassionate use. Some companies establish a lottery system to determine which patients will have treatment access.
3. Requesting compassionate use access to a drug from the FDA
If a company agrees to grant your child compassionate use, then congratulations! You and your physician must next seek approval from the Food and Drug Administration of the compassionate use application. The FDA reports that of the over 1,200 compassionate use requests granted by companies that it considered in 2015, it approved 99.5%. Moreover, FDA medical officers sometimes identify other drugs that would be appropriate for a patient to try instead of the drug for which a compassionate use access is being requested. Extremely rarely, FDA might determine that there is not sufficient evidence of the safety and effectiveness of the investigational drug you are applying for.
There are two forms that your physician can use when applying to the FDA for a compassionate use. Form 1571 is posted on the FDA website. However, many physicians have expressed concern that Form 1571 takes 8-16 hours to complete. In response to these complaints, in 2015 the FDA developed a new “short form,” Form 3926, which is intended to take physicians 45 minutes to complete. Although this form has not been officially finalized, FDA officials will accept it.
FDA states that emergency requests, when access to the drug is needed immediately due to a life-threatening situation, may be submitted over the phone or electronically, with paperwork to follow within 15 days.
Unlike companies, which have full discretion when reviewing compassionate use requests, the FDA has a very specific set of standards that must be met for a compassionate use application to be granted:
• A patient must have a serious or life-threatening disease or condition, with symptoms that have a substantial impact on day-to-day life. Cancer belongs to this category.
• A child should be not eligible to enroll in a clinical trial of the drug due to medical history, poor health, age, or some other reason.
• There should be no other effective approved alternative treatment to diagnose, monitor, or treat the disease or condition.
• The potential benefits to a child of trying an unapproved drug must justify the potential risks of the medication, such as side effects, and the risks should be reasonable considering the health of the child. The benefits will be determined by your physician and stated in the application to the FDA.
The timing of FDA action, which can take just a few hours in emergency cases and up to 30 days for less urgent requests, depends on the complexity of a case and how much the drug has been studied.
Recently, some states have passed Right to Try Laws that permit companies to provide patients access to unapproved drugs without the consent of the FDA. In fact, it is highly unlikely that these new laws would be of assistance to you because drug companies, not FDA, are the main gatekeepers to compassionate use. These laws do nothing to force or incentivize companies to provide unapproved drugs on a compassionate use basis.
4. Requesting compassionate use access to a drug from your hospital
The third step in the application process is to obtain approval from the Institutional Review Board of your child’s hospital, which serves as an ethics committee protecting people who participate in medical research. The IRB will require and review an informed consent document which states that a patient is aware of and is willing to accept potential risks associated with the drug, including unknown risks.
In an emergency, defined as a life-threatening situation in which no standard acceptable treatment is available and in which there is not sufficient time to obtain IRB approval, in rare cases treatment with a compassionate use drug may begin without prior IRB approval, and the IRB must be notified of the emergency treatment within 5 working days of the start of treatment.
If your physician does not have access to an IRB, there are independent commercial IRBs which can review the compassionate use application for a cost.
Costs to you of your child’s treatment with a compassionate use drug
Drug companies may only charge you the manufacturing cost of the drug. In fact, companies very rarely charge a fee because it does not reflect the drug’s market price. While FDA warns that most insurance companies do not cover the costs of using an unapproved drug, this might not be the case for your child. You may or may not have to pay for additional medical care related to use of the unapproved drug, such as administration of the drug and monitoring.