Despite the implementation of the new European rules, the feared fall of clinical trials did not occur in 2023. However, the 21st National Report on Clinical Trials of Medicinal Products, published by the Italian Medicines Agency, describes a varied context. The sector has been affected by the full application of Regulation (EU) No 536/2014, with the adoption of more complex organisational arrangements. There has been a decrease in the number of trials in almost all EU Member States, but also signs of resilience. In particular, the progressive trend analysis shows that Italy has not lost ground, with 611 clinical trials authorised in 2023. 

Robert Nisticò: “Italy has ensured that the system is well-maintained. Dialogue with all stakeholders to be encouraged”
“The data of the Report give us an overall light and shadow picture: initial difficulty is to be expected in applying different and more complex organisational methods. However, Italy has managed to ensure that the system is well-maintained, even if not in a homogeneous way for the various types of trials", says AIFA’s President, Robert Nisticò. "In detail, the profit trials sector has benefited the most from administrative simplifications. Non-profit research has proven to be less robust, not only in Italy, but also throughout the European Union; moreover, it was already clear in 2022 that non-profit sponsors would suffer the greatest setbacks. Precisely to better manage these potential problems – continues Nisticò – in 2023, a series of initiatives designed for the non-profit sector were activated by the network of European Agencies, together with the European Commission and the EMA, also involving stakeholders (patients first) in order to help make the European scenario more attractive”.

Pierluigi Russo: “Clinical trials as a driver of the country’s development”
“We cannot be satisfied with the substantial stability of clinical trials in Italy. Moving the focus from the figures to the broader perspective of European and international competition, the picture that emerges from the Report shows ample room for improvement - says AIFA's Technical Scientific Director, Pierluigi Russo - The trend of phase I clinical trials is stable at 11-18%, with a number of trials in the last 10 years far lower than in Germany, France, UK and Spain. The conditions must be created for the potential of our research centres to meet the industrial context, scaling the paradigms of biomedical research up to the level of economic and social development. We can and must do more to regain attractiveness and performance. The regulatory environment can contribute to this: in 2024, AIFA issued two guidelines dedicated to research and clinical trials.”

2023, a year of change
In Italy, 2023 was the year of the expected reform of the Ethics Committees, which have grown to 40 local and 3 national committees. To be initiated, a clinical trial must have been authorised by AIFA, which includes the favourable conclusions of the Ethics Committee. 
The clinical trials evaluated in 2023 in Italy were 764: of these, 80% were authorised (611), while only 4.6% received a refusal. Of the 611 authorised trials, 524 (85.8%, 88.7% in 2022) are international and 87 (14.2%, 11.3% in 2022) are national. Therefore, there is a slight recovery in national trials (+2.9%), despite remaining below the pre-pandemic level, when they were around 20%.

Trials by therapeutic area
Oncology still represents the lion’s share. In 2023 the largest number of authorised trials was concentrated in the oncology and haemato-oncology sectors, reaching 34.7% of the total, down compared to 39.9% in 2022 (-5.2%). This is followed by clinical studies on diseases of the nervous system (11.1%), up 2.8% compared to the previous year; diseases of the immune system (8.5%), cardiovascular system (6.2%), blood and lymphatic system (6.1%) have also slightly increased. 2023 showed again a reduction in studies on viral diseases, which have been steadily decreasing since 2021. The top ten therapeutic areas include gastrointestinal diseases (4.1%), neonatal pathologies and abnormalities (3.9%), both of which have slightly increased. Diseases of metabolism and nutrition (3.3%) and those of the musculoskeletal system (2.8%) are at the bottom of the list. 
    
Rare diseases 
Clinical trials in the field of rare diseases accounted for 30.6% of the total (187 out of 611), a 7% decrease compared to 2022. However, international non-profit trials have grown from 1 study in 2022 to 14 in 2023 (from 0.4% to 7.5%), while international profit trials remain above 80%.

Profit and non-profit sponsors    
In general, in the four-year period 2020-2023, 2764 trials were authorised in Italy, with a clear prevalence of profit sponsors. In 2023, 82.7% of approved clinical trials (505) were sponsored by pharmaceutical companies, compared to 17.3% (106) by hospitals, universities, IRCCS (research and healthcare institutes), scientific associations, foundations, local health authorities (ASL). The gap is narrowing compared to 2022, when profit studies peaked at 85%, with non-profit studies falling to an all-time low (15%). The share of profit trials remains predominant, but the 2023 data suggest a possible rebalancing between the two sectors, with a slight recovery of non-profit trials, crucial to ensure greater diversification in clinical research objectives. Finally, 19 compassionate use programmes were also launched in 2023; 4 of them concerned oncology indications.

The trend of the last 20 years
The report also reconstructs the progress of the clinical trials authorised from 2000 to 2023. After the four years 2006-2009, when the number of authorisations remained constantly above 750, with a peak of 880 in 2008, in the following decade it remained around 600-700. The increasing adoption of ‘complex’ trials, bringing together in one trial two or more studies that would have been submitted separately in the past, seems to have contributed to the reduction in the overall number of studies submitted. 
2021 was an exceptional year, with 818 trials, returning to levels not seen in more than a decade. This reflects the desire to make up for the time lost due to the pandemic. In the last two years, figures have returned to average and, in particular, 2023 recorded a 7.8% decrease compared to 2022, a trend common to many EU countries. This reduction seems to reflect the impact of the new management model introduced by Regulation (EU) No 536/2014, which required an inevitable adjustment period.