Early access to medicines in development

Some facts about compassionate use

Compassionate Use vs Off-label use

'Compassionate use' is the technical term used to indicate a treatment option that allows the use of an unauthorised medicine outside a clinical study in individual patients under strictly controlled conditions. 'Compassionate use' differs from 'off-label' use. In 'off-label' use a licensed medicinal product is prescribed for an indication, or to a patient for which the product is not specifically licensed, whereas, in 'compassionate use' the medicinal product is not licensed and not used as a treatment for any disease.

Compassionate Use programmes in Europe

In Europe there are certain criteria to compassionate-use programmes (1). It only applies to patients who have a life-threatening disease with no satisfactory authorised therapies or who cannot enter a clinical trial (e.g. because they are outside the inclusion criteria). Furthermore, the medicinal product concerned must either be the subject of a marketing authorisation application, or under evaluation in a clinical trial. (1)

The compassionate use programme thus helps to make medicines that are still under development available to patients before they are approved. It should be mentioned that the clinical development of medicines serves to establish that newly developed medicines are effective and safe. Therefore, there is a risk that the medicines used in compassionate use programmes turn out not to be safe or effective. The risks of taking potentially unsafe and/or ineffective medicines have to be balanced with the risk of doing nothing for progressive diseases.

How compassionate use is implemented in different EU countries

Compassionate use programmes are coordinated and implemented by the individual EU Member States, which decide independently how and when to open such programmes according to national rules and legislation. Doctors who wish to obtain a promising medicine for one of their seriously ill patients will need to contact the relevant national authority in their respective country and follow the procedure that has been set up. The national authority keeps a register of the patients treated with the medicine within the compassionate use programme, and systems are in place to record any side effects reported by the patients or their doctors.

Compassionate use programmes are governed by legislation in individual EU Member States, to make medicines available on a named-patient basis or to cohorts of patients. It will differ per country who is responsible (physician or license holder), what the programme is called, which authorities coordinate compassionate use, if and how adverse events and efficacy have to be reported and if and how compassionate use is reimbursed. (2)

Since many treatments for rare neuromuscular disorders are state of the art and complex drugs, they are generally quite expensive. For some countries reimbursement will be through national or local systems (e.g. ATU in France covers the costs of the medicines for French patients in compassionate use programmes), while for other countries, patients have to pay for the medicines themselves (which for rare diseases is often not possible due to the expensive nature of the medicines). It is also possible that the company provides the medicines to the patients free of charge through charity programmes.

Due to the different implementation, legislation and reimbursement of compassionate use in different EU countries, access to compassionate use programmes differs for patients based on where they live. Ideally, a pan-European system should be in place to allow equal access to all.

Access to medicines under development other than Compassionate Use or participation in a Clinical Trial

Doctors can also obtain promising medicines for their patients by requesting a supply of a medicine from the manufacturer, to be used for a patient under their direct responsibility. This is often called treatment on a 'named-patient basis' and should not be confused with compassionate use programmes. In this case, the doctor responsible for the treatment will contact the manufacturer directly. While manufacturers do record what they supply, there is no central register of the group of patients that are being treated in this way.

Sometimes patients can enter 'expanded access programmes' (also called open label studies, or extension studies). A company that makes a promising medicine may choose to run one of these programmes to allow early access to their medicine and to widen its use to patients who can potentially benefit from it. For example, patients who have been treated with the medicine during a clinical trial and wish to continue treatment may be able to do so via an expanded access programme. These programmes are often authorised by national authorities in the same way as clinical trials, and patients are followed in the same way as patients in a clinical trial.

Compassionate use vs clinical trial participation

Participation in placebo-controlled clinical trials may be another way to receive treatment with medicines that are in development before they are approved. A certain number of patients participating in a placebo-controlled trial will receive a placebo rather than the medicine that is being evaluated, so this is no guarantee to have access to drug during the trial. Nevertheless, sometimes the trial will have an expanded access programme to ensure access to the medicine after the patient has completed the clinical trial. Furthermore, without patients willing to participate in clinical trials it is impossible to develop treatments. Also here the disclaimer applies that treatments that are in clinical development may not be safe or effective.


(1) European Regulation 726/2004/EC legislates for 'compassionate use' programmes in the European Union. http://www.ema.europa.eu/ema/index.jsp?curl=pages/regulation/general/general_content_000293.jsp



(2) http://www.trialsjournal.com/content/11/1/104
(Table 2 of this paper summarizes the differences between different countries in Europe)

12 Apr 2017