Classification and performance of drug observational studies
On 8 August 2024, AIFA published Decree no. 425/2024. The scope of this Decree, considering the different legal and regulatory framework between clinical trials and observational studies, is to provide all the information required in order to prevent that a trial is erroneously classified as observational study and vice versa.
What is an observational study?
An Observational Study is a clinical study where patients’ exposure to a specific therapeutic strategy is not preliminarily decided by the study protocol, but falls into the current clinical practice and the prescription of a treatment is clearly separated from the decision to include a patient in the study.
If a therapeutic strategy provides for the use of medicinal products prescribed according to the authorized therapeutic indication and based on the normal clinical practice, these studies are defined as “observational pharmacologic studies”.
Observational studies, depending on the moment when data are detected in regard to what happens in reality, can be either retrospective (the study examines events that have already occurred), transversal (data collection and concerned event are contextual), prospective (the study examines concerned events in time, as they occur).
To summarize, an observational study, in order to be classified as such, should meet the following conditions:
- the drug must be prescribed and administered under the conditions of use authorized for the marketing in Italy;
- the prescription of the drug under examination is part of the normal clinical practice;
- the decision to prescribe the drug to the individual patient should come before and be independent from the decision to include the subject in the study;
- diagnostic and evaluation procedure should comply with the current clinical practice, with no additional burden for the patients following their participation in the study and with no further burden for the NHS following its performance;
Which are the types of observational studies?
An observational study can have a prospective, retrospective, two-direction, transversal (real time analysis of prevalence data) design.
- A prospective study includes a prospective collection of data on patients falling into the population characteristics, therapeutic indications and strategy as described in the study protocol.
- A retrospective study is designed in order to collect and process data on patients already undergoing a therapeutic strategy, by a secondary collection and analysis of the relevant clinical data.
- In a two-direction study the two previous designs both apply.
- A transversal study is referred to an accurate observation of data in a specific moment (prevalence study) where all information is generated with a single observation at the starting point of the study.
Pharmacogenetics and pharmacogenomics studies should also be considered as observational studies requiring the carrying out of analyses for pharmacogenetic/genomics evaluations on biologic samples withdrawn during the normal clinical practice.
What should be done to start a study?
Every observational study should be founded on a study protocol where the aspects listed below must be clearly assessable:
- research hypothesis
- definition of the primary and secondary goals;
- expected results;
- observational study type;
- selection of the sample size;
- information to be collected;
- any involvement of the facility and/or health professionals;
- resources requested and funding source;
- terms to participate;
- information addressed to the subjects, including an authorization by the subjects for the use of their data, for the sole purposes indicated by the protocol and in compliance with the regulations on privacy;
- terms for the data publication.
The study protocol and the whole documentation required by annex I of the Decree, should undergo an official evaluation by the Unique Ethics Committee, identified by the Sponsor among one of the Territorial or national ethic committees. In case of a multicenter study, the Sponsor shall find a unique Ethic Committee, to be charged with the study evaluation.
Moreover, the obligation to notify all drug observational studies to AIFA via the Observational Study Register (RSO) still applies, according to the terms indicated by AIFA.
Where can observational studies be carried out?
Observational studies can be carried out by public health facilities (or by similar facilities), universities, private health facilities, clinics of General Practitioners and/or Pediatricians or freelance doctors, referring to the Ethic Committee to be selected by the Sponsor for any notification and/or approval applications.
For all other facilities not expressly listed above (e.g. territorial pharmacies, other health facilities, or data collection via decentralized digital devices) the performance of a drug observational study will be evaluated by the Ethic Committee and, if necessary, by AIFA, with special reference to the PASS/PAES studies, to verify the suitability of the staff and facilities to be involved based on the proposed protocol.
Is the study result publication mandatory?
Upon submission of the study, a commitment should be clarified and described by the Sponsor to draft a final report and to make the results public at the end of the investigation, even in case of negative results.
Di Renzo Regulatory Affairs is a consulting company specialized in supporting companies operating in the field of human medicinal products.
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Written on 22/08/2024 by Felisiano Cipressi
