2. Early access: Comparisons | EUPATI Open Classroom

6. Comparisons

Compassionate use should not be confused with 'named-patient basis' treatments, which see doctors obtain medicines directly from companies before authorisation. This is done on an individual basis under the direct responsibility of the doctor, and the EMA does not need to be informed.

In general, medicines that are not yet authorised are first made available through clinical trials and patients should always be considered for inclusion in clinical trials before being offered compassionate use programmes.

Table 1: High level comparison of early access provision in the US and Europe

Criteria	EAP (US)	CU (EU)	NP (EU)
Applicable legislation	Expanded access prorammes (FDA 1997)	Art. 83 (1) Reg. (EC) No 726/2004	Art. 5 Dir. (EC) 2001/83
Who initiates?	Company Physician	Company applies to MS (opinion possible by CHMP)	Doctor requests from company
Criteria to define/select target population by…	Company/FDA	Company /CHMP	Company /Doctor
Who benefits? Limitations in use?	Group of patients (treatment INDs & protocols) Named patient (single patients IND)	Group of patients	Only named patients for whom the physician has made a request
Liability	Company	Company	Prescribing doctor
Medicine in clinical trial or under assessment for MA?	Yes	Yes	No
Off-label use permitted?	No	No	Yes
Are doctors paid for participating?	Yes	No	No
Are medicines in programme priced?	No	No	Yes (possible)

Adapted from: Patil S. Early access programs: Benefits, challenges, and key considerations for successful implementation. Perspect Clin Res 2016; 7: 4-8.

Table 2: Exemplary comparison of compassionate use and named-patient access provisions in three countries of the European Union


	Named Patient Programme	Compassionate Use Programme	Named Patient Programme	Compassionate Use Programme	Early access to medicines scheme
Type	Individual patient	Groups/ cohorts of patients	Individual patient	Groups/ cohorts of patients	Individual patient	Groups/ cohorts of patients
Responsible Agency	Federal Institute for Drugs and Medical Devices (BfArM) Paul Ehrlich Institute (PEI)		French National Agency for medicines and Health Products Safety (ANSM)		Medicines and Healthcare products regulatory Agency (MHRA) for benefit/risk scientific opinion; National Institute for Health and Care Excellence (NICE)
Initiator	Treating physician	Company	Prescribing doctor	Company	Prescribing doctor	Company
Duration	Up to 1 year, renewable, until MA and marketed		1 year, renewable possible (renewal application latest 2 months before expiration)		12 to 18 months with 3-monthly review
Pricing & Reimbursement	Product supplied free of charge		Free pricing and full reimbursement possible if there is a valid Cadre de prescription compassionelle (CPC) Difference to price negotiated at launch to be paid back (fines possible if difference is significant)		Product supplied free of charge
Restrictions & Requirements			Rare or serious diseases with no appropriate treatment alternatives available in France Treatment cannot be delayed Product is likely to offer benefit or significant advantage over and above existing options Potential adverse reactions are likely to be outweighed by benefits
	Patients should enrol in Clinical Trials where possible	- Medicine must be in Clinical Trials in Germany or abroad - Must be able to show product safety, indicative efficacy, medical need and urgency - Must involve a severe illness that has a lasting negative impact on an individual’s Quality of life - No conventional treatment option. - MAH must give their consent to off-label use Efficacy and safety for patient presumed not the object of a clinical research no appropriate treatment Efficacy and safety for patient presumed presumed innovative must inform patients about noncompliance with the MA, the existence of a CPC and the risks involved and benefits likely to be obtained with the medicine Adverse event reporting mandatory			Although the company will record what is supplied, there is often no central register for treated patients	Applicant is able to supply product in each region of the UK

Germany: Compassionate Use Programs were initiated in Germany in 2010. While the process for the cohort programme is more complex than the named-patient programme, it grants the company a higher degree of control such as limiting the medication to a particular patient subgroup.

France: The Temporary Utilisation Program (ATU) has been in place since 1992; latest revision and renaming 2021: ATU is changed to ‘autorisation d’accès précoce (AAP)’, for NP ‘Compassionate access authorisation (autorisation d’accès compassionnel (AAC)’. Reimbursement opportunities make compassionate use programs in France potentially the most attractive in Europe.

UK: The Early Access to Medicines Scheme programme (EAMS) was launched in 2014 in the UK. The application process for companies requires submission of a dossier with the latest available data, and evidence requirements for both regulatory purposes and NICE appraisal, thus potentially contributing to the data required for MA application and subsequent assessment.