What is a compassionate use programme?
A compassionate use programme (CUP) provides access to a medicinal product as a treatment for patients who have no other suitable options. This programme allows doctors to request the use of a medicine that is still being evaluated and not yet fully approved.
CUP is for patients with chronic or severely debilitating diseases, or those facing life-threatening conditions. These patients cannot be adequately treated with approved medicines. The doctor applies for this special access to the pharmaceutical company developing the product and seeks approval from national authorities.
According to European legislation (for medicines authorised through the central procedure), the medicine in question must be either undergoing clinical trials or have an application for marketing authorisation. This means it doesn’t need to be authorised anywhere else in the world. If the medicine is being tested in clinical trials for your specific disease, your doctor can request access through compassionate use.
Most EU Member States and many other European countries have specific processes for compassionate use, but they may vary in complexity and time required. These programmes offer hope and an opportunity for patients who have limited treatment options to potentially benefit from promising medicines.
These programmes are only put in place if the medicine is expected to help patients with life-threatening, long-lasting or seriously debilitating illnesses, which cannot be treated satisfactorily with any currently authorised medicine. The medicine must be undergoing clinical trials or have entered the marketing-authorisation application process and while early studies will generally have been completed, its safety profile and dosage guidelines may not be fully established. – Extract of the EMA Q&A document on compassionate use
What a compassionate use programme is not:
A compassionate use programme has a specific purpose and should not be confused with other scenarios. Here are some important distinctions:
- Not an experiment or clinical trial: A compassionate use programme is not an experiment or clinical trial. Patients receive the medicine as a treatment, not for testing purposes. It is intended to provide a potential option when no other suitable treatments are available.
- Not a substitute for product development: Compassionate use programmes cannot replace clinical trials. They are not experiments. It cannot be concluded whether the product is safe and effective on a group of patients. A CUP can be organised in parallel to clinical trials, but it can only be authorised if clinical trials are already in progress, and recruitment in a CUP should not be an obstacle to the recruitment of patients in clinical trials (for example if patients prefer to receive the medicine on a compassionate basis and not take the risk of receiving a placebo).
- Not an off-label use: Compassionate use only applies to medicines not yet authorised for any condition. Off-label use refers to using authorised medicines in different ways than indicated on the label.
- Not a financial aid or humanitarian programme: Financial aid or humanitarian programmes are for authorised medicines that patients cannot afford. Compassionate use programmes, on the other hand, are for medicines still under evaluation, not yet on the market.
- Not a means to pre-market authorisation: Compassionate use should not be exploited to promote a product or gain a market advantage. It requires proper authorisation and monitoring by national competent authorities and cannot be used for commercial purposes or investigational activities.
- Not a “favour” for clinicians: Compassionate use should not be offered as a reward to clinicians for high patient enrolment in clinical trials. Such practices can lead to inequities in accessing compassionate use medicines and are not recommended.
Compassionate use programmes are designed to provide hope and potential treatments for patients facing serious health challenges and limited options. They serve as an essential bridge between experimental medicines and full approval for use, offering patients a chance for improved outcomes and quality of life.
Can anyone access medicines on a compassionate basis?
Before a medicine is approved and available on the market, it goes through rigorous evaluations to ensure its effectiveness and safety. Clinical trials are the primary method to gather this information. In most cases, compassionate use is reserved for patients who cannot participate in clinical trials.
Compassionate use provides access to the actual medicine, not a placebo. The patient receiving it is expected to benefit from the treatment. In contrast, clinical trials involve testing the medicine against another treatment, which could be a placebo. Specific biomedical criteria determine who can participate in clinical trials, and some patients may be excluded based on predefined conditions.
For instance, patients who are severely ill with multi-organ impairment or significant liver or kidney issues are often excluded from clinical trials. However, they may still receive the treatment through compassionate use. This ensures that the most seriously ill patients receive optimal care and do not take the risk of receiving an ineffective treatment or placebo. Even if it’s uncertain whether the treatment will be beneficial, if there’s a chance it could work, patients should have the opportunity to receive it.
Regulators can authorise compassionate use on a named-patient basis, where the doctor makes a specific request for a particular patient, or for a group of patients (cohort). In a cohort compassionate use, regulators define the eligible patient population for the programme. For example, if there are only two available medicines for a certain disease, regulators might limit the compassionate use programme to patients who have already tried both medicines without success or who cannot tolerate either product.
Compassionate use serves as a lifeline for patients with no other treatment options and offers hope for improved health outcomes when traditional clinical trials are not feasible.
Is there an unlimited supply of medicines that can be used for compassionate use?
The availability of a medicine for compassionate use is not unlimited. It depends on the stage of development and production capacity of the company developing the medicine.
During the early stages of development, the company produces small quantities of the product for laboratory and animal testing. When the medicine progresses to human clinical trials, the quantities remain limited, typically involving a few dozen to a few hundred patients.
As the product advances and shows promising results, the company may decide to conduct larger confirmatory trials and prepare for marketing authorisation. This is known as the Go/No-Go decision. At this point, the company needs to produce larger quantities of the medicine to accommodate thousands of patients in clinical trials.
During this phase, there is a period when larger quantities of the medicine become available. However, it is essential to note that there might be limitations in meeting the high demand for compassionate use during this transitional period. The company needs time to build a manufacturing site and validate production quality.
Once the medicine is fully authorised and production capacity increases, the company should be better equipped to meet the demand for compassionate use. However, there might be a brief period of uncertainty during the transition from limited production to larger-scale availability.
It’s essential to understand that compassionate use is intended for patients with no other treatment options, and the availability of the medicine may vary based on the stage of development and production capacity. Companies work diligently to meet the needs of patients while ensuring the safety and effectiveness of their products.
When demand is too high
In January 1996, demand for a new HIV treatment (HAART) was extremely high, but manufacturers couldn’t meet it immediately. To ensure fairness, patients were selected via a random process using a computer-based lottery system. This approach aimed to include all eligible patients gradually and alleviate the impact of limited supply. “Since patients will be selected randomly by computer, there will be no conscious or unconscious emotional preference or pressure. Drawing lots will relieve doctors of the responsibility of choice and preserve patients’ trust in their attending physicians. Lots will be drawn each time supplementary drug doses are made available, with the aim of including all eligible patients.”
Main characteristics of compassionate use programmes in different EU Member States:
- Timing: Compassionate use programmes are typically initiated late in the developmental process of medicinal products, bridging the time between the end of phase III development, regulatory approval, and product launch. However, some CUPs can start earlier, even at the end of phase I trials.
- Cost: Some CUPs are provided for free, while others may have associated costs. In some countries, companies are prohibited from charging for compassionate use, while in others, the decision is left to the company’s discretion.
- Duration: Compassionate use programmes are usually authorised for one year and can be renewed. However, they cannot last indefinitely, and a marketing authorisation application must be prepared and submitted eventually.
- Scope: CUPs are intended for medicinal products that aim to treat, prevent, or diagnose serious or rare diseases when there are no available therapeutic alternatives for some or all patients.
- Efficacy Data and Benefit Claims: There is no consensus on requiring efficacy/benefit data as a prerequisite for authorising compassionate use. Since CUPs run alongside clinical trials, not all data may be available at the time of authorisation. However, the benefit for the group of patients should be plausible based on earlier trials.
- Consent Form: Patients receiving treatment through compassionate use often need to read and sign a consent form that explains what is known and not known about the medicine. The form highlights the importance of reporting any responses, both positive and negative, while taking the medicine. The healthcare professional remains responsible for prescribing the treatment.
Type of CUP, procedure and review times for 7 Member States
| Country | CUP type | Regulatory process | Review times |
|---|---|---|---|
| France | Cohort or named patient | Well defined | Named patient: 24-48h Cohort: 2-4 months |
| Denmark | Cohort or named patient | Well defined | Within 3-4 weeks |
| Germany | Cohort or named patient | Under change | 2-3 months |
| Italy | Cohort or named patient | Well defined but complex | Named patient: 1 month Cohort: not defined |
| The Netherlands | Cohort or named patient | Well defined | Named patient: 4 weeks Cohort: not defined |
| Spain | Cohort or named patient | Need local expertise | Very variable, case by case |
| United Kingdom | Named patient | Well defined | 4 weeks after receipt of notification of intent to import |
- Adapted from Helene Sou, Pharm Med 2010; 24(4):1-7
How to import, who pays, legal basis for 7 Member States
| Country | Import authorisation | Payer | Legal basis |
|---|---|---|---|
| France | Nominative ATU authorisation taken as import permitCohort ATU requires import permit | Hospital or national insurance. 100% covered | Code de la Santé Publique (Art. L.5121-12 and R.5121-68 to 76) |
| Denmark | Imported by pharmacy | Hospital/patient co-payment. Reimbursement as for approved products | Lov om laegemidler no. 1180 as amended 17 June 2008 |
| Germany | Import permit required | Company | 14 and 15 ArzneimittelGesetz Novelle |
| Italy | Ethics committee written approval required | Hospital or national insurance | Decreto 8 maggio 2003; Legge 648/1996 |
| The Netherlands | Import permit required | Patient/company Usually not reimbursed | Art. 40.3c Geneesmiddelenwet van 25 Juni 2007. Circular 2002-06-IGZ |
| Spain | Need to apply for importation to the national agency | Company | Real Decreto 1015/2009; Ley 29/2006 (Art. 24) and Real Decreto 223/2004 (Art. 28) |
| United Kingdom | Import permit required | Reimbursement case by case, price can be set freely | SI 1994 no. 3144 |
- Adapted from Helene Sou, Pharm Med 2010; 24(4):1-7