Drugs, Aifa: two new guidelines for clinical trials and observational studies - Agenzia Nova (2024)

Two guidelines to simplify the organization of clinical trials of drugs and regulate observational studies. Those that after the marketing are used to evaluate the actual level of efficacy and safety on large numbers of patients, but also the actual impact of any new authorized therapeutic indications. An activity that is extended to online data collection, wearables and other wearable and non-wearable devices. With a careful eye on the autonomy of the studies, setting strict limits on the compensation provided for research staff. The Italian Medicines Agency (AIFA) - reports a note - has approved the two documents providing clarifications with respect to the current European and national legislation and also adapting the Italian context to the EU Regulations. "An important step forward not only for the evaluation of the use and safety profile of medicines in normal conditions of use, but also for the verification of their prescribing appropriateness and for the evaluations of a drug-economic type that can provide a solid basis when renegotiating prices. Possibly rewarding those who have shown greater efficacy than what was proven by clinical trials or, otherwise, determining a reduction in prices that generates useful savings to be reinvested in more innovative drugs", comments the president of AIFA, Robert Nisticò.

The document reiterates first of all the four conditions for classifying a study as "observational": the drug must be prescribed and administered under the conditions of use authorized for marketing in Italy, even if retrospective studies are permitted for the evaluation of any compassionate or off-label use, i.e. for therapeutic indications other than those originally authorized; the prescription of drugs must be part of normal clinical practice; the decision to prescribe them to the individual patient must be prior to and completely independent of the study; the diagnostic and evaluation procedures must correspond to current clinical practice, without additional costs, both for patients and for the National Health Service (NHS). But the guidelines also emphasize the ethics and transparency of the studies. In fact, it is mandatory that AIFA always receives notification of the study through the appropriate Register and that the Ethics Committee receives a formal request for evaluation. This is to verify: the ethics and scientific nature of the research, transparency of sponsorships and results, any costs incurred, so that no additional expense weighs on the funds of the National Health Service. And speaking of transparency, the guidelines specify that "any compensation provided for research staff must be communicated to the Ethics Committee" and be "commensurate with the actual commitment required by the structure and in any case of such a value as not to influence the work of the personnel involved".

Observational studies can be conducted at public and private healthcare facilities, universities and general medicine and pediatrician practices. For other facilities, the conduct of a study will be assessed by the Ethics Committee. There is no mandatory evaluation by AIFA for observational pharmacological studies, which may however enter into the merits of the studies themselves if "particular critical issues or incongruities are identified with respect to the declared observational nature". This with particular reference to uses other than those for which the drug was originally authorised. The guidelines represent "clarifications and an integration of what has already been described in the guidance documents drawn up on the subject within the European regulatory network". Technological and scientific evolution, as well as the complexity of clinical trials, may require the support of third-party service providers that the experimental site may not be able to provide. Starting from this, the AIFA guidelines list the necessary requirements to be able to avail of "external" support.

First of all, the roles and responsibilities of the trial sponsor and the trial site must be distinct and outlined regarding the management of the service provider and the principal investigator retains ultimate responsibility for the study, therefore he must in any case have complete information on all decisions. The service provider must also be "adequately trained on the study protocol". Reimbursement of expenses for food, accommodation and transportation of trial participants is permitted. Reimbursement is also extended to the accompanying person in the event of inability to travel alone. Reimbursements can also be provided through a service provider. Compensation for loss of earnings is permitted exclusively in the case of healthy volunteers and in the cases provided for by EU Regulation no. 536 of 2014. The same Regulation provides that the costs of experimental drugs, auxiliary drugs and medical devices used for the purposes of the trial are not to be borne by the participant, but remain borne by the pharmaceutical company promoting the study.