The Assessment of the Innovativeness of a New Medicine in Italy

Abstract

Objectives: Starting from April 2017, the Italian Medicine Agency (AIFA) has approved new criteria for defining any new medicinal product with an innovative indication. The purpose of the study is to analyze the activity of innovativeness evaluation according to the new approach, to estimate the weight of each criterion considered for innovativeness definition, and to evaluate how the new approach works in terms of consistency and reproducibility.Methods: A retrospective analysis was performed on the final reports evaluating the drug innovativeness assessment published on the AIFA's website between April 2017 and January 2021. Descriptive statistics, chi-square test, whether the conditions were respected, or Fisher's exact test was used to explore the association between characteristics of drugs and the innovativeness status and the association between the three criteria. Profiles of the decision process and their relationship with innovativeness response were described. In order to evaluate the weight of each criterion in predicting the innovativeness status, a Classification Tree (CT) algorithm was applied.Results: Overall, of the 109 published drugs reports, 37 (33.9%) were recognized as fully innovative, 29 (26.6%) were considered conditionally innovative, while for 43 (39.4%) reports innovativeness was not recognized. Considering the three criteria of the decision process, the added therapeutic value was the only criterion statistically associated with a drug's degree of innovation (p < 0.001). The therapeutic need and the quality of clinical evidence were statistically associated (p = 0.008) even if only a mild association was observed. The added therapeutic value was the most important variable in predicting the innovativeness status according to the classification tree (CT) model applied, achieving an accuracy of 89.4%. No difference was found between orphans and non-orphan drugs or oncological and non-oncological drugs.Discussion: The added therapeutic value is the most important criterion of the multidimensional approach for the innovativeness status definition of a new medical product. A mild association was found between the therapeutic need and the quality of evidence. Overall, similar decision profiles bring the same evaluation of innovativeness status, indicating a good consistency and reproducibility between decisions.

The Evaluation of Drug Innovativeness in Italy: Key Determinants and Internal Consistency

“…Two papers have recently been published on this topic [ 13 , 14 ]. Findings in these papers, in alignment with ours, showed that added therapeutic value is the most influential parameter, followed by GRADE evaluation, and that variables other than the criteria used for these appraisals do not influence decisions taken by AIFA’s CTS.…”

“…Findings in these papers, in alignment with ours, showed that added therapeutic value is the most influential parameter, followed by GRADE evaluation, and that variables other than the criteria used for these appraisals do not influence decisions taken by AIFA’s CTS. In these two papers, the key drivers of drug innovativeness appraisal were scrutinized using a deterministic [ 13 ] and probabilistic [ 14 ] approach. The deterministic decision tree had several methodological limitations, since the model did not fit all the decisions taken.…”

“…In Italy, the criteria introduced in 2017 to appraise innovativeness are in alignment with those most often cited in the literature, including unmet need, added therapeutic value, and quality of the evidence provided [ 12 , 13 ]. Unmet need and added therapeutic value are ranked using a five-level scale (maximum, important, moderate, poor and absent) [ 14 ]. The quality of the evidence is ranked through a four-level scale (high, moderate, low, very low), known as the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) method [ 15 ].…”

Do France, Germany, and Italy agree on the added therapeutic value of medicines?

“…Marketing authorization holders may apply for any new indication to be recognized as innovative, that is, a tag that allows the indication to claim some access benefits: a dedicated fund that covers the expenditure in the first three years and immediate access to the regional markets. Evaluation of innovativeness is based on three criteria: the therapeutic need (based on the value of the alternatives), the added therapeutic value (ATV), and the quality of the evidence provided (11;12). The final evaluation for those medicines that claim innovative status, unlike that of all the other drugs, is made publicly available (13).…”

Value assessment of medicinal products by the Italian Medicines Agency (AIFA) and French National Authority for Health (HAS): Similarities and discrepancies

“…Article 1 paragraph 402 requires the AIFA to establish the criteria for the classification of innovative drugs (oncologic and not) ( 11 ). The innovation evaluation model [at label (European Medicines Agency, EMA) therapeutic indication] proposed by the AIFA consists of a multidimensional approach based on three criteria ( 12 ): (1) unmet therapeutic need, (2) therapeutic added value (TAV), and (3) quality of evidence (GRADE methodology) ( 13 – 15 ). The therapeutic need is conditioned by the therapies available for the specific disease in question, and it indicates to what extent the new therapy is necessary to satisfy the therapeutic needs of the patients ( 12 ).…”