Compassionate use is a treatment option that allows the use of an unauthorised medicine. Compassionate-use programmes are for patients in the European Union (EU) who have a disease with no satisfactory authorised therapies or cannot enter aclinical trial. They are intended to facilitate the availability to patients of new treatment options under development.
Compassionate-use programmes are often governed by legislation in individual EU Member States, to make medicines available on a named-patient basis or to cohorts of patients.
In addition to this, EU legislation provides an option for Member States to ask the European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) to provide an opinion to all EU Member States on how to administer, distribute and use certain medicines for compassionate use. The CHMP also identifies which patients may benefit from compassionate-use programmes. This is described in Article 83 of Regulation (EC) No 726/2004
and is complementary to national legislation.
The objectives of Article 83 are to:
- facilitate and improve access to compassionate-use programmes by patients in the EU;
- favour a common approach regarding the conditions of use, the conditions for distribution and the patients targeted for the compassionate use of unauthorised new medicines;
- increase transparency between Member States in terms of treatment availability.
More information is available in:
- Questions and answers on the compassionate use of medicines in the EU
- Guideline on compassionate use of medicinal products, pursuant to Article 83 of Regulation (EC) no 726/2004
Compassionate-use opinions from the CHMP
| Name of medicine | Ledipasvir/Sofosbuvir |
|---|---|
| Active substance | ledipasvir, sofosbuvir |
| Dosage | 90mg / 400 mg |
| Pharmaceutical form | Film coated tablet |
| Member State notifying the Agency | Ireland |
| CHMP opinion documents | Conditions of use, conditions for distribution and patients targeted and conditions for safety monitoringSummary on compassionate use |
| Date of opinion | 20/02/2014 |
| Company contact information | Gilead Sciences Limited Granta Park Abington Cambridgeshire CB21 6GT United Kingdom Tel. +44 (0)208 5872206 Fax +44 (0)1223 897233 E-mail: eamemed.info@gilead.com |
| Status | Ongoing |
| Related documents | – |
| Name of medicine | Daclatasvir |
|---|---|
| Active substance | daclatasvir |
| Dosage | 30 and 60 mg |
| Pharmaceutical form | Film coated tablet |
| Member State notifying the Agency | Sweden |
| CHMP opinion documents | Conditions of use, conditions for distribution and patients targeted and conditions for safety monitoringSummary on compassionate use |
| Date of opinion | 21/11/2013 |
| Company contact information | Bristol-Myers Squibb Pharma EEIG Uxbridge Business Park Sanderson Road Uxbridge UB8 1DH United Kingdom Tel. +44 (0)1895 523 740 Fax +44 (0)1895 523 677 E-mail: medical.information@bms.com |
| Status | Ongoing |
| Related documents | – |
| Name of medicine | Sofosbuvir Gilead |
|---|---|
| Active substance | Sofosbuvir |
| Dosage | 400 mg |
| Pharmaceutical form | Film-coated tablet |
| Member State notifying the Agency | Sweden |
| CHMP opinion documents | Conditions of use, conditions for distribution and patients targeted and conditions for safety monitoring Summary on compassionate use |
| Date of opinion | 24/10/2013 |
| Company contact information | Gilead Sciences International Ltd Granta Park, Abington Cambridgeshire CB21 6GT United Kingdom Tel. +44 (0)1223 897496 Fax +44 (0)1223 897233 E-mail: eamemed.info@gilead.com |
| Status | Ongoing |
| Related documents | – |
| Name of medicine | IV Zanamivir |
|---|---|
| Active substance | Zanamivir |
| Dosage | 10 mg/ml |
| Pharmaceutical form | Solution for infusion |
| Member State notifying the Agency | Sweden |
| CHMP opinion documents | Conditions of use, conditions for distribution and patients targeted and conditions for safety monitoring Summary on compassionate use |
| Date of opinion | 18/02/2010 |
| Company contact information | GlaxoSmithKline Research & Development Limited 980 Great West Road, Brentford Middlesex TW8 9GS United Kingdom Tel. +44 (0)20 8047 5000 or +44 (0)20 8990 3885 E-mail: julie.c.kerrison@gsk.com |
| Status | Ongoing |
| Related documents | – |
| Name of product | Tamiflu IV |
|---|---|
| Active substance | Oseltamivir phosphate |
| Dosage | 100 mg |
| Pharmaceutical form | Powder for solution for infusion |
| Member State notifying the Agency | Finland |
| CHMP opinion documents | Conditions of use, conditions for distribution and patients targeted and conditions for safety monitoring Summary on compassionate use |
| Date of opinion | 20/01/2010 |
| Company contact information | F. Hoffmann-La Roche Ltd. Pharmaceuticals Division PBMV Bldg 74/3O 104 CH-4070, Basel Switzerland Tel. +41 61 688 5522 Fax +41 61 687 2239 E-mail: basel.tamifluquestions@roche.com |
| Status | Closed |
| Related documents | Public statement on Tamiflu IV: Closure of compassionate-use programme in the EU Tamiflu IV compassionate-use programme EMEA/H/K/002287 – Closure of programme |
Expanded access (also known as compassionate use) refers to the use of an investigational drug outside of a clinical trial by patients with serious or life-threatening conditions who do not meet the enrollment criteria for the clinical trial in progress. Outside the US, such access is allowed through Named patient programs. In the US this type of access may be available, in accordance with United States Food and Drug Administration (FDA) regulations, when it is clear that patients may benefit from the treatment, the therapy can be given safely outside the clinical trial setting, no other alternative therapy is available, and the drug developer agrees to provide access to the drug. The FDA refers to such a program as an expanded access program (EAP).[1] EAPs can be leveraged in a wide range of therapeutic areas including HIV/AIDS and other infectious diseases, cancer, rare diseases, and cardiovascular diseases, to name a few.
There are several types of EAPs allowed in the United States. Treatment protocols and treatment INDs provide large numbers of patients access to investigational drugs. A single-patient IND is a request from a physician to the FDA that an individual patient be allowed access to an investigational drug on an emergency or compassionate use basis.[2] When the FDA receives a significant number of requests (~10 to 100) for individual patient expanded access to an investigational drug for the same use, they may ask the trial sponsor to consolidate these requests, creating an intermediate-size group.[3] “Compassionate use” is a more colloquial term that is not generally used by the FDA.
FDA regulations
Since 1987, the FDA has had rules in place that have enabled patients, under specific circumstances, to access drugs or biologics that are still in development for treatment purposes. These expanded access program rules were amended in 2009 by the FDA to ensure “broad and equitable access to investigational drugs for treatment.”[4]
The regulations include the following:[4]
- Criteria that must be met in order to authorize the expanded access use
- Requirements for expanded access submissions
- Safeguards to protect patients and the clinical trial process
The regulations also include general criteria for granting expanded access:[3]
- The patient must have a serious condition or disease for which there is no comparable alternative therapy available
- The patient must be unable to participate in a clinical trial
- The potential benefit must outweigh the potential risk of using the treatment
- There should be no impact on the completion of the clinical trial or the drug’s approval
Despite the updated regulations, debate remains over key elements of expanded access:
- Deciding at what point in the clinical trial process access should be given. Some stakeholders support expanded access programs after phase I testing in clinical trials. The FDA has stated that most drugs should not be eligible until some point during phase III when efficacy data have been obtained, unless compelling phase II data on safety and efficacy are available.[3][5]
- Weighing risks to the patient against the potential benefits. The FDA requires that a physician and an institutional review board (IRB) determine that a treatment will not pose undue risk to the patient, relative to the condition he or she is suffering from.[6] However, the FDA maintains the right to overrule the physician and IRB.[3]
- Determining who should get access. The FDA states that expanded access should only be considered for patients with a serious disease or condition, but the FDA’s rules do not provide a definition of “serious”; instead it provides examples of diseases and conditions that fall into this category.[3] In the case of a cancer drug, the sponsor of an expanded access program must define exactly which patients will get access. Most often, access is limited to those patients with the same type of cancer the drug is being tested for.[7]
A number of challenges can exist when patients seek access to investigational drugs:
- Obtaining an IRB review. Finding time on an IRB’s schedule can be difficult, particularly for doctors who are not based at research centers where IRBs are readily available. The fee for the review may pose a problem as well. It may be unclear who is responsible for the cost of the IRB review, which can be as much as $2,000. Many IRBs conduct reviews pro bono but others that charge will often only waive their fees for research done in their hospital.[6][8]
- Protecting physicians against liability risk. Currently, physicians may be concerned that they could face a liability risk for investigational drugs that they recommend to patients or help them gain access to, potentially discouraging them from doing so. The FDA does not have jurisdiction over this issue but there is a bill in Congress, the Compassionate Access Act of 2010 (H.R. 4732), that would address the situation.[6][8][9]
- Paying for the drug. While the FDA allows drug companies to recover the costs of providing a treatment through an EAP, many companies may hesitate to do so because it requires disclosing the cost of their drug, which is often a closely guarded secret. In addition, many insurance companies won’t cover the costs of experimental treatment so access could be limited to patients with the means to pay for it.[6][8]
- Assessing the potential impact of adverse events on drug development. Adverse events (AEs) that result from expanded access programs must be reported to the FDA in the same way AEs are reported in the case of a clinical trial. The FDA states that, to their knowledge, no drug candidate has been turned down for approval because of an adverse event that appeared in an expanded access program.[3][6]
Outside the United States
Outside the U.S., programs that enable access to drugs in the pre-approval and pre-launch phase are referred to by a variety of names including “named patient programs,” “named patient supply” and “temporary authorization for use.”[10] In the EU, named patient programs also allow patients to access drugs in the time period between centralized European Medicines Agency (EMEA) approval and launch in their home countries which can range from one year to eighteen months.[11]
References
- Jump up^ US National Cancer Institute – Access to Investigational Drugs accessed April 22, 2007
- Jump up^ FDA Final Rules for Expanded Access to Investigational Drugs for Treatment Use and Charging for Investigational Drugs
- ^ Jump up to:a b c d e f Final FDA Rules on Expanded Access to Investigational Drugs for Treatment Use
- ^ Jump up to:a b FDA website
- Jump up^ Expanded Access to Investigational Drugs Genetic Engineering & Biotechnology News, January 15, 2010.
- ^ Jump up to:a b c d e Access to Investigational Drugs Remains Challenge Despite New FDA Rules ‘’The Pink Sheet’’
- Jump up^ Managing Access to Drugs Prior to Approval and Launch ‘’Life Science Leader’’[dead link]
- ^ Jump up to:a b c FDA webinar accessed May 5, 2010
- Jump up^ FDA Law Blog accessed May 5, 2010
- Jump up^ Helene S (2010). “EU Compassionate Use Programmes (CUPs): Regulatory Framework and Points to Consider before CUP Implementation”. Pharm Med 24 (4): 223–229.
- Jump up^ [Ericson, M., Harrison, K., Laure, N. & De Crémiers, F., Compassionate Use Requirements in the Enlarged European Union. RAJ Pharma, May 2005: 83.
External links
- Early/Expanded access for medial devices from the US FDA
- Guidelines for Expanded Access Protocols from BC (Canada) Cancer Agency
- Preapproval Opportunities. Applied Clinical Trials, June 2008.
- Boundaries of Expanded Access. Pharmaceutical Executive, May 2008.
- A Time for Compassion. Applied Clinical Trials, September 2007.
- Cancer Patients Deserve Faster Access to Life-Saving Drugs. Wall Street Journal, May 2, 2009.
- Fighting for a Last Chance at Life. New York Times, May 16, 2009.
- Expanded Access to Investigational Drugs Genetic Engineering & Biotechnology News, January 15, 2010.
- Meeting Global Demand for Investigational Drugs Life Science Leader, December 2009.
