Background The introduction of human epidermal growth factor receptor 2 (HER2)-targeted treatment options, including dual HER2 blockade, has improved the prognosis for patients with HER2-positive breast cancer (BC) substantially. However, most of these treatments are administered via the intravenous (IV) route, which can present many challenges, such as long infusion and observation times, issues associated with repeated IV access, and increased strain on time and resources of medical centers and healthcare professionals. A fixed-dose combination of pertuzumab and trastuzumab for subcutaneous (SC) injection (pertuzumab, trastuzumab, and hyaluronidase-zzxf (PHESGO^®, F. Hoffmann-La Roche Ltd, Basel, Switzerland; PH FDC SC)) has been approved for use alongside chemotherapy for early-stage and metastatic HER2-positive BC. Objectives This systematic literature review was performed to identify evidence relating to time/resource use and resulting cost differences between SC and IV administration of oncology biologics in a hospital setting, and, ultimately, to inform economic modeling and associated health technology assessment of PH FDC SC. Methods Electronic databases (Embase, MEDLINE, and EconLit) were searched on 9 April 2020. Additional hand searches were performed to identify publications not captured in the electronic database search. Publication screening and data extraction (study characteristics, participants, interventions, costs, and time/resource use) were carried out per the standard Cochrane review methodology. The quality of economic evidence of cost analyses was assessed using the 36-item checklist of the National Institute for Health and Care Excellence Single Technology Appraisal Specification for submission of evidence (January 2015). Results The database search identified 2,740 records, of which 237 underwent full text screening. Full text screening, prioritization of publications about patients with a cancer diagnosis, and the addition of four citations identified during the hand search resulted in 72 final included publications, relating to 71 unique studies. This included 40 publications that described the time/resource use and/or costs associated with SC versus IV trastuzumab administration for the treatment of HER2-positive BC, and 28 publications that described time/resource use and/or costs associated with rituximab SC versus IV administration for the treatment of non-Hodgkin’s lymphoma/follicular lymphoma and diffuse large B-cell lymphoma. The majority of publications showed substantial time savings for preparation and administration of SC versus IV therapy, and cost savings associated with reductions in healthcare professional time and resource use for SC administration. Limitations There was a lack of consensus between publications regarding time and cost measurements. In addition, the search was limited to publications related to anticancer drugs; the majority of the studies included were performed in European countries. Conclusions and implications This review indicated a substantial body of evidence showing time/resource and cost savings of SC versus IV administration of oncology biologics in a hospital setting, which can be used to inform economic evaluations of PH FDC SC.

Background: Alzheimer’s disease (AD) causes progressive decline of cognition and function. There is a lack of systematic literature reviews on prognostic and predictive factors in its early clinical stages (eAD), i.e., mild cognitive impairment due to AD and mild AD dementia. Objective: To identify prognostic factors affecting eAD progression and predictive factors for treatment efficacy and safety of approved and/or under late-stage development disease-modifying treatments. Methods: Databases were searched (August 2022) for studies reporting prognostic factors associated with eAD progression and predictive factors for treatment response. The Quality in Prognostic Factor Studies tool or the Cochrane risk of bias tool were used to assess risk of bias. Two reviewers independently screened the records. A single reviewer performed data extraction and quality assessment. A second performed a 20% check. Content experts reviewed and interpreted the data collected. Results: Sixty-one studies were included. Self-reporting, diagnosis definition, and missing data led to high risk of bias. Population size ranged from 110 to 11,451. Analyses found data indicating that older age was and depression may be associated with progression. Greater baseline cognitive impairment was associated with progression. APOE4 may be a prognostic factor, a predictive factor for treatment efficacy and predicts an adverse response (ARIA). Elevated biomarkers (CSF/plasma p-tau, CSF t-tau, and plasma neurofilament light) were associated with disease progression. Conclusions: Age was the strongest risk factor for progression. Biomarkers were associated with progression, supporting their use in trial selection and aiding diagnosis. Baseline cognitive impairment was a prognostic factor. APOE4 predicted ARIA, aligning with emerging evidence and relevant to treatment initiation/monitoring.

Background: Alzheimer’s disease (AD) is the most common type of dementia, causing progressive decline of memory, thinking, and behavior, impairing daily functioning. Early AD (eAD) includes mild cognitive impairment (MCI) due to AD and mild AD dementia. Objective: The aim of this study was to investigate symptomatic treatment prevalence and treatment patterns in eAD. Methods: Embase, MEDLINE, and EBM Reviews were searched in November 2021 for observational studies reporting symptomatic treatment patterns in eAD. The range of patients receiving treatment was collated. Risk of bias was assessed using the Joanna Briggs Institute (JBI) prevalence tool. Two independent reviewers screened the records, one performed data extraction and quality assessment while a second checked. Results: Twenty-one studies (prospective and retrospective cohorts, cross-sectional studies, and a survey) were included. Population size ranged from 23 to 2,028. Worldwide, 18 to 35% of patients diagnosed with MCI due to AD received any AChE inhibitor (three studies; n = 631), 7 to 8% memantine (two studies; n = 229), and 9% combination therapy (one study; n = 402). Patients receiving no treatment ranged from 41 to 54% (two studies; n = 733). Worldwide, in mild AD dementia patients, 13 to 89% received any AChE inhibitor (six studies; n = 3,715), 1 to 21% memantine (five studies, n = 3,527), and 0.4 to 39% combination therapy (four studies, n = 3,018). Patients receiving no treatment ranged from 9 to 26% (five studies, n = 4,073). Conclusion: Limitations in reporting led to unclear risk of bias. The results reveal a pattern of use of symptomatic treatment in eAD beyond approved labels and highlights the opportunity for new consensus guidelines to inform clinical practice.

Background: This work aimed to determine the role and action points for the involvement of medical societies in the European Health Technology Assessment (EU HTA) Methods: An online pre-convention survey was developed addressing four areas related to the EU HTA: (i) medical societies’ role; (ii) role of clinical guidelines; (iii) interface with the European Society for Medical Oncology Magnitude of Clinical Benefit Scale (ESMO-MCBS); and (iv) approaching ‘best-available evidence’ (BAE). A descriptive analysis of questionnaire outcomes was conducted to inform the European Access Academy (EAA) Fall Convention 2023. Within the working groups (WGs), action points were identified and prioritised. Results: A total of 57 experts from 15 countries responded to the survey. The WGs were attended by (i) 11, (ii) 10, (iii) 12, and (iv) 12 experts, respectively, representing a variety of national backgrounds and stakeholder profiles. The most relevant action points identified were as follows: (i) incorporation of clinical context into population, intervention, comparator, outcomes (PICO) schemes, (ii) timely provision of up-to-date therapeutic guidelines, (iii) ensuring the inclusion of MCBS insights into the EU HTA process, and (iv) considering randomized controlled trials (RCTs) as the gold standard and leveraging regulatory insights if development programs only include single-arm trials. Conclusions: The involvement of medical societies is a critical success factor for the EU HTA. The identified key action points foster the involvement of patient associations and medical societies.

Background: We examined four potential challenges for the implementation of the European Union (EU) Regulation 2021/2282 on Health Technology Assessment (EU HTAR): interaction with the European Medicines Agency (EMA), expert input, the interface of European health technology assessment (EU HTA) joint procedures with those within Member States, and the management of conflict of interest. This research aims to explore how to address these challenges in a balanced manner and prioritise key actions for effective collaboration in the context of the EU HTA. Methods: The methodology included a pre-convention survey among relevant stakeholders as well as working groups and the plenary ranking of discussion outcomes at the European Access Academy (EAA) Spring Convention 2024. Results: In the survey, 65.5% of respondents indicated that experts are currently not sufficiently included in the upcoming joint scientific consultations and clinical assessments; only 37.9% suggested that the EU HTA joint procedures would accelerate national appraisal decision-making, and 58.6% believed that the principles of ‘transparency’ and ‘competency’ are balanced in the EU HTA position on conflict of interest. The top priority action points identified in the working groups were the involvement of the best available expertise, the early and inclusive involvement of experts, strengthened early scientific dialogue, and the fostering of the political willingness/financial support of EU Member States to increase capacities. Conclusions: The key topics identified were an approach to conflict of interest that balances transparency obligations and the need for expertise, strengthens the involvement of clinical and patient experts, intensifies early interaction between the EMA and EU HTA, and increases the involvement of the EU Member States.

Meloxicam is a non-steroidal anti-inflammatory drug used in the treatment of rheumatoid arthritis, osteoarthritis and other inflammatory diseases. However, its prolonged use is associated to several side effects like gastrointestinal perforations, ulcerations and bleeding, probably due its low aqueous solubility and wettability after oral administration. These side effects can reduce patient compliance and discourage physician from prescribing this drug. In this way, inclusion complexes between meloxicam and methyl-β-cyclodextrin were prepared in aqueous solution by phase solubility studies and in solid state by freeze-drying method in order to increase drug solubility. The physicochemical characterization of the prepared complexes in solid state was performed by different techniques. Furthermore, hydrogels containing poloxamers were prepared for topical administration of meloxicam. For this purpose, solid inclusion complexes were incorporated in hydrogels with different poloxamers composition. The rheological behaviour of these formulations was studied by different methods and the drug release from optimised hydrogels was evaluated by Franz diffusion cells, applying some mathematical models to analyse the drug release mechanism from hydrogels. Results from phase solubility studies showed the formation of inclusion complexes between meloxicam and methyl-beta-cyclodextrin in aqueous solution in a 1:1 stoichiometry and an increase in drug solubility. Different techniques employed indicated complete formation of complexes in solid state prepared by the freeze-drying method. Moreover, the performed set of rheological studies, easily adapted to similar systems, demonstrated that hydrogels containing poloxamers and cyclodextrin may provide a suitable supramolecular platform for meloxicam delivery as a novel strategy to increase drug bioavailability.