Expanded access

Expanded access or compassionate use is the use of an unapproved drug or medical device under special forms of investigational new drug applications (IND) or IDE application for devices, outside of a clinical trial, by people with serious or life-threatening conditions who do not meet the enrollment criteria for the clinical trial in progress.

These programs go under various names, including early access, special access, or managed access program, compassionate use, compassionate access, named-patient access, temporary authorization for use, cohort access, and pre-approval access.^[1][2][3]

In general the person and their doctor must apply for access to the investigational product, the company has to choose to cooperate, and the medicine's regulatory agency needs to agree that the risks and possible benefits of the drug or device are understood well enough to determine if putting the person at risk has sufficient potential benefit. In some countries the government will pay for the drug or device, but in many countries the person must pay for the drug or device, as well as medical services necessary to receive it.

In the US, compassionate use started with the provision of investigational medicine to certain patients in the late 1970s, and a formal program was established in 1987 in response to HIV/AIDS patients requesting access to drugs in development. An important legal case was Abigail Alliance v. von Eschenbach, in which the Abigail Alliance, a group that advocates for access to investigational drugs for people who are terminally ill, tried to establish such access as a legal right. The Supreme Court declined to hear the case, effectively upholding previous cases that have maintained that there is not a constitutional right to unapproved medical products.

As of 2016,^[update] regulation of access to pharmaceuticals that were not approved for marketing was handled on a country by country basis, including in the European Union, where the European Medicines Agency issued guidelines for national regulatory agencies to follow. In the US, Europe, and the EU, no company could be compelled to provide a drug or device that it was developing.^[1]

Companies sometimes provide drugs under these programs to people who were in clinical trials and who responded to the drug, after the clinical trial ends.^[2][3]

In the US, one of the earliest expanded access programs was a compassionate use IND that was established in 1978, which allowed a limited number of people to use medical cannabis grown at the University of Mississippi, under the direction of Marijuana Research Project Director Dr. Mahmoud ElSohly. It is administered by the National Institute on Drug Abuse.^{[citation needed]}

The program was started after Robert C. Randall brought a lawsuit (Randall v. U.S)^[13] against the FDA, the Drug Enforcement Administration, the National Institute on Drug Abuse, the Department of Justice, and the Department of Health, Education & Welfare. Randall, who had glaucoma, had successfully used the Common Law doctrine of necessity to argue against criminal charges of marijuana cultivation that had been brought against him, because his use of cannabis was deemed a medical necessity (U.S. v. Randall).^[13] On November 24, 1976, federal Judge James Washington ruled in his favor.^{[14]: 142 [15]}

The settlement in Randall v. U.S. became the legal basis for the FDA's compassionate IND program.^[13] People were only allowed to use cannabis under the program who had certain conditions, like glaucoma, known to be alleviated with cannabis. The scope was later expanded to include people with AIDS in the mid-1980s. At its peak, fifteen people received the drug. 43 people were approved for the program, but 28 of the people whose doctors completed the necessary paperwork never received any cannabis.^[16][14] The program stopped accepting new people in 1992 after public health authorities concluded there was no scientific value to it, and due to President George H. W. Bush administration's policies. As of 2011, four people continued to receive cannabis from the government under the program.^[17]

The closure of the program during the height of the AIDS epidemic led to the formation of the medical cannabis movement in the United States, a movement which initially sought to provide cannabis for treating anorexia and wasting syndrome in people with AIDS.^[18]

In November 2001 the Abigail Alliance for Better Access to Developmental Drugs was established by Frank Burroughs in memory of his daughter, Abigail.^[19] The Alliance seeks broader availability of investigational drugs on behalf of people with terminal illnesses. It is best known for a legal case, which it lost, Abigail Alliance v. von Eschenbach, in which it was represented by the Washington Legal Foundation. On August 7, 2007, in an 8–2 ruling, the U.S. Court of Appeals for the District of Columbia Circuit reversed an earlier ruling in favor of the Alliance.^[20] In 2008, the Supreme Court of the United States declined to hear their appeal. This decision left standing the appellate court decision that people who are terminal ill patients have no legal right to demand "a potentially toxic drug with no proven therapeutic benefit".^[21]

In March 2014, Josh Hardy, a 7-year-old boy from Virginia, made national headlines that sparked a conversation on pediatric access to investigational drugs when his family's request for brincidofovir was declined by the drug manufacturer, Chimerix.^[22] The company reversed its decision after pressure from cancer advocacy organizations, and Josh received the drug that saved his life.^[23][24] Hardy later passed away in September 2016 due to complications related to his underlying cancer diagnosis.^[25] In 2016 Kids v Cancer, a pediatric cancer advocacy organization, launched the Compassionate Use Navigator to assist physicians and guide families about the application process.^[26] Since then, FDA simplified the application process, but stressed that it cannot require a manufacturer to provide a product.^[27][28] FDA receives about 1,500 expanded access requests per year and authorizes 99% of it.^[29]

• Orphan drug
• Right-to-try law
• Emergency Use Authorization