Proposed new regulation on observational studies of medicinal products


The Ministerial Memorandum no. 6 of 2 September 2002 (Ministry of Health) sets forth the current regulatory requirements for observational (i.e. non-interventional) studies of drugs in Italy. Such studies are defined as studies centred on aspects and diseases where the drug is prescribed to patients according to its approved indication, as a part of normal clinical practice, and where the decision to prescribe the drug is independent of the decision to include the patient in the study. The current regulation provides that particular care must be adopted in drafting the protocols for observational studies, certain rules applicable to clinical trials must apply also to such studies (e.g. the rules on transparency of sponsorship, ownership and disclosure of data, informed consent and privacy of the patients), and notice of the study must be given to the local Ethics Committee.

The regulation has proven to be inadequate and unclear however, in particular as to the criteria to be adopted by the Ethics Committees for the evaluation of the protocols of those studies. In addition, certain Italian Regions (e.g. Lombardy and Tuscany) have enacted regionally applicable guidelines for the filing and evaluation of the protocols of such studies. As a consequence it is difficult for sponsors, Ethics Committees and medical centres to interpret and implement the current rules. Accordingly, the regulatory framework needs to be improved.

The Ministry of Health and AIFA (Italian Drugs Agency) have issued draft guidelines for the classification and conduct of observation studies on drugs and launched a public consultation process that ended in October 2007. The results of the public consultation are expected to be published soon and the draft guidelines could be enacted at national level in the near future.

In summary, the draft guidelines provide more guidance to the interested parties as to i) when a study is to be considered an observational study, ii) the protocol’s requirements for such a study, iii) the reporting procedures for adverse drug reactions; iv) the medical centres and physicians under whose control a study may be conducted; v) the rules for sponsorship and insurance of the study, vi) the rules for the disclosure of the results of the study.

The draft guidelines also provide for the implementation of a national registry of the observational studies and provide clear instructions to sponsors and Ethics Committees of the procedural and operational implications of (i) the presentation to the Ethics Committees (including the list of documents to be presented) and (ii) launch of such studies.

The table below summarises the major points contained in the draft guidelines.

Type of observational study


Notification to EC

Request of EC Approval

Documents to be presented

Prospective cohort studies




· Sponsor’s Declaration (nature of the study);

· Protocol

· List of information to be collected

· Details of the Investigator and the centre

· List of participant centres and investigators (in case of multi-centric study)

· Costs of the study

· Source of financing of study

· Notice of rights and consent for data protection purposes[1]

· Description of measures adopted to protect the confidentiality of the information

· Proposed agreement with the centre in relation to the financial aspects of the study

· Payments to investigators (if any)

Other observational studies of etiological nature

a) retrospective cohort studies

b) case control studies

c) case cross over studies

d) transversal studies

e) ecological studies




Descriptive studies

a) appropriateness studies





[1] Only for studies where there is a direct relationship with the patients