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Background: Inclusion of patient-reported outcomes (PROs) in oncology clinical trials is strongly recommended. However, selecting the most appropriate patient-reported outcome measures (PROMs) is not easy. This study aimed to develop a breast cancer (BC) specific comprehensive archive of PROMs. Methods: As part of the PRO4All project, we identified available PROMs in oncology by searching facit.org, eortc.org, eprovide.mapi-trust.org, PubMed, ema.europa.eu (European Public Assessment Reports) and published reviews. For this analysis, only BC tools were extracted. We described information about PROM name, type of questionnaire, questionnaire variant(s), recall period, number of items, and presence of minimum clinically important difference (MCID) reference in literature. Then, we assigned each item to a specific domain according to a predefined taxonomy of 38 items for outcome classification. Results: We identified and analyzed 383 PROMs. Of these, 29 were BC specific, but 2 were excluded because the questionnaires description was not available. 6 (22.2 %) were variants of another questionnaire. All questionnaires were self-reported. In 6 cases (22.2 %) the recall period to consider was the “last week”. The mean number of items per questionnaire was 25.81 (range 6–71). 602 items were assigned to an outcome domain: emotional functioning/wellbeing in 26.6 % of cases, physical functioning in 14.1 %, delivery of care in 10.8 %, and general outcomes in 10.5 %. MCID reference was found only in 4 (14.8 %) cases. Conclusions: The newly developed archive represents a useful tool to optimize the use of PROMs in the evaluation of treatments in BC patients, promoting a patient-centered approach both in clinical research and practice.

Abstract 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.

The attention paid by regulatory authorities to patient-reported outcomes (PROs) and their related measures (PROMs) has progressively increased to allow for a more complete description of the patient’s health status. This work aimed at investigating the use of PROs/PROMs in relation to reimbursement agreement and innovativeness recognition by the Italian Medicines Agency (AIFA). The list of European Public Assessment Reports (EPARs), downloaded from the European Medicine Agency (EMA) website, was analyzed to identify drugs authorized between 2017 and 2021. The associations between the use of PROs/PROMs in the EPARs and the reimbursement and innovativeness status in Italy were explored through Chi2 test and logistic regression. In addition, each innovativeness report was analyzed to identify any further evidence about the consideration of PROs/PROM in the decision-making process. Of the 403 EPARs analyzed, 197 (48.9%) reported the use of PROs/PROMs. A subsample of 229 drugs with a reimbursement class (A, H, or C) officially assigned by AIFA was further investigated. Of them, 49.3% reported the use of PROs/PROMs. The Chi2 test revealed a statistically significant association between the use of PROs/PROMs and innovativeness (p = 0.001) and orphan status (p = 0.012). In the logistic regression, orphan status and availability of PROs/PROMs are significant predictors of the innovativeness status. However, of the 46 innovative drugs, only 9 (19.6%) explicitly reported a consideration of a PRO/PROM in their innovativeness reports. Robust instrument’s validation, reliable data collection and growing potential’s awareness are keys to increase the consideration of PROs at every step of the drug development process.