Data from the rapid mortality surveillance system in 19 major Italian cities were used to carry out a timely assessment of the health impact of the COVID-19 epidemic. By 18 April, a + 45% excess in mortality was observed, with a higher impact in the north of the country (+ 76%). The excess was greatest among men, with an increasing trend by age. Surveillance data can be used to evaluate the lockdown and re-opening phases.

Background: Standardized mortality surveillance data, capable of detecting variations in total mortality at population level and not only among the infected, provide an unbiased insight into the impact of epidemics, like COVID-19 (Coronavirus disease). We analysed the temporal trend in total excess mortality and deaths among positive cases of SARS-CoV-2 by geographical area (north and centre-south), age and sex, taking into account the deficit in mortality in previous months. Methods: Data from the Italian rapid mortality surveillance system was used to quantify excess deaths during the epidemic, to estimate the mortality deficit during the previous months and to compare total excess mortality with deaths among positive cases of SARS-CoV-2. Data were stratified by geographical area (north vs centre and south), age and sex. Results: COVID-19 had a greater impact in northern Italian cities among subjects aged 75-84 and 85+ years. COVID-19 deaths accounted for half of total excess mortality in both areas, with differences by age: almost all excess deaths were from COVID-19 among adults, while among the elderly only one third of the excess was coded as COVID-19. When taking into account the mortality deficit in the pre-pandemic period, different trends were observed by area: all excess mortality during COVID-19 was explained by deficit mortality in the centre and south, while only a 16% overlap was estimated in northern cities, with quotas decreasing by age, from 67% in the 15-64 years old to 1% only among subjects 85+ years old. Conclusions: An underestimation of COVID-19 deaths is particularly evident among the elderly. When quantifying the burden in mortality related to COVID-19, it is important to consider seasonal dynamics in mortality. Surveillance data provide an impartial indicator for monitoring the following phases of the epidemic, and may help in the evaluation of mitigation measures adopted.

Since January 1995, all European Union applications for marketing approval for medicinal products derived from biotechnology and other drugs considered potentially innovative follow the EMEA centralized procedure. In order to assess the overall degree of therapeutic innovation of these drugs, we considered, for each approved agent, its target, the availability of previous treatments and the extent of its therapeutic effect. The following scores for therapeutic innovation were assigned through a consensus process: 'A' (important), 'B' (moderate) and 'C' (modest). The overall degree of important/moderate therapeutic innovation was 47% of all therapeutic agents (32% important; 15% moderate). Most (80%) of the EMEA-approved therapeutic agents were for serious diseases. The remaining ones were for risk factors (7%) or nonserious diseases (13%).

What is already known about this subject We recently proposed an algorithm to assess the degree of therapeutic innovation of new therapeutic agents. It was based on the disease seriousness, the availability of previous treatments and the extent of the therapeutic effect, and was applied to all therapeutic agents approved by the EMEA in the period 1995–2003. A low percentage (32%) of important therapeutic innovation was found. This figure may be an underestimate of the actual level of innovation, because common biotechnological products, such as recombinant human insulins, must follow the centralized procedure. What this study adds Details for each agent, focusing on the comparison of the degree of therapeutic innovation between biotechnological and nonbiotechnological therapeutic agents approved by EMEA during the its first decade of activity (1995–2004). The underlying hypothesis was that the latter have a higher degree of innovation because they followed the centralized procedure on the assumption that they are innovative. The percentage of important therapeutic innovation was low not only for biotechnological products (25%), as expected because they include many already known products such as insulins, but also for nonbiotechnological therapeutic agents (29%). Aims In a previous paper, we proposed an algorithm to assess the degree of therapeutic innovation of the agents approved by the European centralized procedure, which must be followed by biotechnological products and is optional for drugs claimed as innovative. A low overall degree of therapeutic innovation (about 30%) was found. This figure may be an underestimate of the actual level of innovation, because common biotechnological products, such as recombinant human insulins, must follow this procedure. To test the hypothesis that therapeutic innovation prevails among nonbiotechnological products, we evaluated separately the degree of therapeutic innovation of biotechnological vs. nonbiotechnological agents in the first decade of European Medicines Agency activity, also studying a possible time trend. Methods We assessed, for each drug: (i) the seriousness of the target disease, (ii) the availability of previous treatments, and (iii) the extent of therapeutic effect according to the previously proposed algorithm. Results Our analysis considered 251 medicinal products corresponding to 198 active substances, classified according to four main areas as therapeutic agents (88.9%), diagnostics (5.5%), vaccines (5.1%) and life‐style drugs (0.5%). Among all therapeutic agents, 49 out of 176 agents (28%) were classified as having an important degree of therapeutic innovation. Fifteen out of 60 biotechnological therapeutic agents were considered important therapeutic innovations (25%), whereas this figure was 29% for nonbiotechnological agents. Conclusions Among active substances claimed as innovative by the manufacturers, only a minority deserve this definition according to our algorithm.