The development of an archive of patient-reported outcome measures (PROMs) in oncology: The Italian PRO4All project.

BACKGROUND: Choosing the most adequate measure of patient-reported outcomes (PROs) for a specific medical condition is not straightforward. This study aimed to develop a comprehensive archive of patient-reported outcome measures (PROMs), observer-reported outcome measures (ObsROMs) and caregiver-reported outcome measures (CROMs) in oncology and identify their main characteristics and target outcome domains. MATERIALS AND METHODS: As part of the Italian PRO4All Project, we retrieved questionnaires through an extensive search of online databases. We developed a data extraction form to collect information on cancer type, questionnaire variant(s), recall period, and scoring system. We performed a content analysis of the questionnaires to assign each item a specific outcome domain according to a predefined 38-item taxonomy. RESULTS: A total of 386 PROMs (n = 356), ObsROMs (n = 13) and CROMs (n = 17) were identified and described; of these, 358 were also analyzed in their content. 47.3 % of the instruments were cancer type-specific, 45.1 % were generic for cancer and 7.9 % were developed for the general population but also recommended in oncology. The great majority (92.2 %) were patient-reported. In 50.3 % the recall period was "last week". The mean number of items per questionnaire was 22.0 (range: 1-130). 7794 items were assigned an outcome domain, the most frequent being emotional functioning/wellbeing (22 %), physical functioning (15.7 %), general outcomes (10.1 %) and delivery of care (8.9 %). CONCLUSIONS: There are a variety of patient and caregiver-reported measures in oncology. This archive can guide researchers and practitioners in selecting the most suitable measures and fostering a patient-centered approach in clinical trials, clinical practice, and regulatory activities.

The Assessment of Patient-Reported Outcomes for the Authorisation of Medicines in Europe: A Review of European Public Assessment Reports from 2017 to 2022.

OBJECTIVES: Health regulators have progressively increased their attention and focus on patient-reported outcomes (PROs), driven by the diffusion of a patient-centred approach to the drug development process. This study investigates the consideration of PROs and their measures (PROMs) in the authorisation of medicines in Europe. METHODS: All medicines for human use authorised or refused by the European Medicines Agency (EMA) in the period 2017-2022 were identified, and corresponding European Public Assessment Reports (EPARs) were downloaded for review. Medicine and PROs/PROM characteristics were systematically recorded. A multivariate logistic regression was performed to identify variables associated with the use of patient-reported evidence in EPARs. RESULTS: Overall, 497 EPARs of authorised medicines and 19 EPARs of refused medicines were analysed; of these, 240 (48.3%) and 10 (52.6%), respectively, reported any use of PROs/PROMs (p = 0.710). For authorised medicines, the likelihood of using PROs/PROMs was negatively affected by generic (OR = 0.01, p < 0.001) and biosimilar status (OR = 0.46, p = 0.013) and positively affected by orphan status (OR = 1.41, p = 0.177). The use of PROMs (50.6% in 2017 vs 47.9% in 2022) did not show a clear pattern over the 6-year period considered (p = 0.758) and was particularly uncommon in some therapeutic areas (e.g., 15.2% in infectious diseases). A total of 816 dyads of PROs/PROMs were identified. On average each EPAR considered 1.6 (range: 0-14) instruments. Patient-reported outcomes were typically secondary (53.3%) and exploratory endpoints (18.8%); in one-third of cases (32.5%), they assessed generic quality of life. Among the PROMs, 227 (27.8%) targeted general population; EQ-5D (11.0%), SF-36/SF-12 (5.9%) and EORTC QLQ-C30 (5.6%) were the instruments most frequently used. CONCLUSIONS: This study suggests PROs/PROMs are considered in less than half of total medicine assessments and even more rarely in some disease areas. The adoption of PROs is key in EMA strategy to 2025 and would be facilitated by consensus development on their measures and optimisation of data collection.

EQ-5D-5L Population Norms for Italy.

OBJECTIVES: This study aimed to provide normative data obtained in response to the EQ-5D-5L questionnaire in Italy and compare this with data from other countries. METHODS: A sample of the Italian adult population (aged ≥ 18 years) was recruited and interviewed online using videoconferencing software (Zoom) between November 2020 and February 2021. The distribution of answers was estimated as per the descriptive system of the EQ-5D-5L, and descriptive statistics were calculated for the EQ VAS score and EQ-5D-5L index value in the whole sample and relevant subgroups. An ordinary least square (OLS) regression was performed to evaluate the impact of sociodemographic variables on EQ-5D-5L results. Lastly, a comparison was made with EQ-5D-5L population norms of other countries. Data analysis was performed using Microsoft Excel and Stata 13. RESULTS: Overall, 1182 people representative of the Italian population (2020) in terms of sex and geographical area responded to the survey. Of the 3125 potential EQ-5D-5L health states, only 106 (3.4%) were selected, and the '11111' and '11112' states were chosen by half of the participants. In terms of EQ-5D-5L dimensions, the frequency of any problems (from slight to extreme) associated with anxiety and depression was high among the very young (18-24 years, 56.0%) and in women of all ages (49.7%). The mean index value (± standard deviation [SD]) was 0.93 (± 0.11) for the entire sample and gradually decreased with age, moving from 0.95 (± 0.06) in the youngest group (18-24 years) to 0.91 (± 0.13) in the oldest age group (≥ 75 years). Similarly, the mean EQ VAS score (± SD) was 81.8 (± 13.5), and decreased from 87.0 (± 8.9) in the 18-24 years age group to 75.1 (± 16.4) among participants > 75 years of age. The existence of self-reported chronic conditions (e.g., cardiovascular disease), female sex, and social assistance recipiency were negatively associated with the EQ-5D index value, while the EQ VAS score was significantly lower in people with chronic conditions and aged > 55 years. Conversely, higher income levels had a positive impact on both the EQ-5D index value and the EQ VAS score. Lastly, both the EQ-5D index value and EQ VAS score in Italy were, on average, higher than in most European countries. CONCLUSIONS: EQ-5D-5L population norms provide useful insights into the health status of the Italian population and can be used as a reference for other surveys using the same instrument.

Early access programs for medicines: comparative analysis among France, Italy, Spain, and UK and focus on the Italian case.

Early access programs (EAPs) generally refer to patient access to medicines/indications before marketing authorization, possibly extended to price and reimbursement approval. These programs include compassionate use, which is usually covered by pharmaceutical companies, and EAPs reimbursed by third-party payers. This paper aims at comparing EAPs in four European countries (France, Italy, Spain, UK) and providing empirical evidence on EAPs in Italy. The comparative analysis was conducted through a literature review (including scientific and grey literature), complemented by 30-min semi-structured interviews with local experts. The Italian empirical analysis employed data available on the National Medicines Agency website. Although EAPs are very different across countries, they exhibit some common features: (i) eligibility criteria refer to the absence of valid therapeutic alternatives and a presumed favourable risk-benefit profile; (ii) payers do not allocate a pre-determined budget to these programs; (iii) total spending on EAPs is unknown. The French EAPs seem to be the most structured, financed through social insurance, covering pre-marketing, post-marketing and pre-reimbursement phases and providing for data collection. Italy's approach to EAPs has been varied, with several programs covered by different payers, including the cohort-based 648 List (for both early access and off-label use), the nominal-based 5% Fund, and Compassionate Use. Most applications to EAPs are from the Antineoplastic and immunomodulating drug class (ATC L). Some 62% of indications in the 648 List are either not under clinical development or have never been approved (pure off-label use). For those subsequently approved, most approved indications coincide with those covered through EAPs. Only the 5% Fund provides data on economic impact (€ 81.2 million in 2021; average cost per patient € 61.5K). Diverse EAPs are a possible source of inequalities in access to medicines across Europe. A harmonization of these programs, though difficult to achieve, could be modelled on the French EAPs and provide key advantages, not least of which a common effort to collect real-world data in parallel with clinical trials and clear separation between EAPs and off-label use programs.