Medicines used in Compassionate Use programs

Programmes can be started if:

• The medicine is subject of an application for a centralised marketing authorisation from the European Commission (clinical trial is still ongoing or the application is still in the proceedings) or the medicine is already authorised, but the programme is run for other indications than authorised.
• The medicine is used for the same indications as in the running clinical trial or as in the application for marketing authorisation.
• The medicine is used
  • as the last treatment option for a life-threatening disease when there are no authorised medicines available  or they have not been effective/tolerated for the patients or
  • for patients with chronic or disabling disease, who cannot be treated with authorised medicines.
• There is no clinical trial running that would be suitable for the patients (no trial running in Estonia, patients are not suitable for the trial or inclusion into the trial has ended).

How to start a programme?

• The medicine has passed successfully phase II clinical trials.
• Initiative for starting a programme can come from the physician or from the manufacturer of medicinal products.  
• Physician/healthcare institution and the manufacturer of medicinal products sign a contract in which among others, they agree upon collection and reporting of safety data.
• Manufacturer of medicinal products provides all the following information to the State Agency of Medicines via e-mail [email protected]:
  • The current summary of clinical trials (safety and efficacy).
  • Indications of the medicine to be used in the programme.
  • Number of patients to be included in the programme and inclusion criteria agreed upon with the physician/healthcare institution.
  • List of healthcare institutions participating in the programme.
  • Information about how the manufacturer of medicinal products is planning to provide the medicine after it has been granted a marketing authorisation, but before it has been reimbursed by the Estonian Health Insurance Fund.
• In a case the application to start CUP is submitted by the representative of manufacturer of medicinal products, the applicant must also present State Agency of Medicines a letter of authority which certifies authorisation given.
• In case the medicine provided via CUP is intended to be used for a single patient, patient’s  physician has to provide State Agency of Medicine the following data via email: [email protected]:
  • Summary of the patient’s disease course
  • Medicines used for the treatment of the patient until that time
  • Medical justification for using the medicine via CUP:
    • Is the medicine neccessary for life saving purposes or for the treatment of severe chronic disease
    • Are there any other suitable treatment options available for the treatment of the patient or are these depleted
    • Is the risk/benefit ratio of the medicine favourable for the patient

• If neccessary, State Agency of Medicines will contact physician(s) of relevant speciality to gain additional information for evaluating the medical justification of the CUP.
• The programme is conducted according to the approved conditions.

During the programme the manufacturer of medicinal products reports to the State Agency of Medicines about:

• Any changes in the programme e.g. plan to include new patients, a marketing authorisation granted by the European Commission, reimbursement granted by the Estonian Health Insurance Fund and ways of providing medicine for patients not applicable for reimbursement.
• Ending of the programme.

Solicited reporting during CUP

The manufacturer of medicinal products/Marketing Authorisation Holder (MAH):

• has to guarantee that a physician records and documents complete and comprehensive case information on adverse reactions* and serious adverse events (GVP IV.C.I.2 and VI.C.I.2.2) and transmits the data to the contact person of the manufacturer of medicinal products/MAH given in the contract signed between manufacturer of medicinal products/MAH and physician or healthcare institution.

* According to the Medicinal Products Act § 786 section 4 a person qualified to prescribe medicinal products is required to inform the State Agency of Medicines of all serious adverse reactions. According to the Medicinal Products Act § 786 section 6 the MAH may be informed of an adverse reaction. It is acceptable that all safety data collected from the programme is reported to the company/MAH for further assessment and collection of the follow-up information.

• has to assess the risks associated to the adverse events. A method of causality assessment should be applied for assessing the causal role of the medicinal products (= adverse reaction) in the solicited adverse events (for example, the WHO-UMC system for standardised case causality assessment).
• Only valid ICSRs of adverse reactions should be reported to EVDAS - ’Post-marketing’ – ’Report from study’ – ’Other studies’ (CUP) or 'Individual patient use’ (NPP) (GVP IV.B.2, VI.C.3., VI.C.4. and VI.C.6.2.3.7). Adverse reactions should be presented and assessed in the periodic safety update report.
• In situations where adverse reactions are suspected to be related to other medicinal products, these reports should be managed, classified and reported as spontaneous ICSRs (Medicinal Products Act §786 and Regulation of the Minister of Social Affairs no 26 § 2.