Introducing new disease-modifying therapies (DMTs) for Alzheimer's disease demands a fundamental shift in diagnosis and care for most health systems around the world. Understanding the views of health professionals, potential patients, care partners and taxpayers is crucial for service planning and expectation management about these new therapies.

To investigate the public's and professionals’ perspectives regarding (1) acceptability of new DMTs for Alzheimer's disease; (2) perceptions of risk/benefits; (3) the public's willingness to pay (WTP).

Informed by the ‘theoretical framework of acceptability’, we conducted two online surveys with 1000 members of the general public and 77 health professionals in Ireland. Descriptive and multivariate regression analyses examined factors associated with DMT acceptance and WTP.

Healthcare professionals had a higher acceptance (65%) than the general public (48%). Professionals were more concerned about potential brain bleeds (70%) and efficacy (68%), while the public focused on accessibility and costs. Younger participants (18–24 years) displayed a higher WTP. Education and insurance affected WTP decisions.

This study exposes complex attitudes toward emerging DMTs for Alzheimer's disease, challenging conventional wisdom in multiple dimensions. A surprising 25% of the public expressed aversion to these new treatments, despite society's deep-rooted fear of dementia in older age. Healthcare professionals displayed nuanced concerns, prioritising clinical effectiveness and potential brain complications. Intriguingly, younger, better-educated and privately insured individuals exhibited a greater WTP, foregrounding critical questions about healthcare equity. These multifaceted findings serve as a guidepost for healthcare strategists, policymakers and ethicists as we edge closer to integrating DMTs into Alzheimer's disease care.

The National Institute for Health and Care Excellence (NICE) has increasingly agreed to reimburse innovative products with high levels of uncertainty as part of managed access agreements (MAAs) while additional data are collected, through the new Cancer Drugs Fund (CDF) or highly specialized technology (HST) pathways. This research aimed to review the data collection stipulations of current MAAs.

We reviewed all current MAAs entered into between NHS England and manufacturers as of 29 October 2018 and key data were extracted.

Twenty-two MAAs were identified (19 through the CDF; three through HST). All MAAs involved an observational data collection component. The source of observational data collection was existing NHS databases (19/22 MAAs: 86.5 percent), existing independent registries (one MAA: 4.5 percent [ataluren]); bespoke MAA registry maintained by manufacturer (1/22 MAA: 4.5 percent [asfotase alfa]), and registries developed as a part of regulatory approval and maintained by the manufacturer (1/22 MAA: 4.5 percent [elosulfase alfa]). Only eight MAAs (asfotase alfa, ataluren, elosulfase alfa, brentuximab vedotin, venetoclax, ibrutinib, daratumumab, and pembrolizumab) had observational data collection as the primary method of data collection. Additionally, 17/22 MAAs (77 percent; all from the CDF) also required ongoing data collection from clinical trials as a key component of the data collection arrangement.

This research identified observational data collection as a requirement in all MAAs, which is primarily through existing registries (except ataluren, which required development of a bespoke registry), while ongoing trial data collection was limited to the CDF. The relatively low cost of using existing registries to fulfil data requirements, with the ability to achieve reimbursement whilst still collecting data from ongoing RCTs, make MAAs an attractive proposition for manufacturers. NICE reportedly plan to increase use of MAAs, with ongoing NICE consultation for changes in the appraisal process potentially allowing expansion to include all indications, which would mean increased opportunities to explore innovative MAAs to support access in the future.

The National Institute for Health and Care Excellence (NICE) may recommend temporary funding through managed access agreements (MAAs) for oncology drugs (via the Cancer Drugs Fund [CDF]) and highly specialized therapies for rare diseases. MAAs allow for the collection of evidence to address key areas of clinical uncertainty, while providing access of medicines to patients, prior to re-appraisal by NICE. Observational data and other real-world evidence (RWE) are crucial requirements for all MAAs and herein we examine the extent these data are being used to inform HTA decisions at re-appraisal.

Existing MAAs entered into between the National Health Service (NHS) England and manufacturers as of 30 October 2018 were identified; for drug:indication pairings with NICE re-appraisals, all information was reviewed and the key data extracted.

Of the twenty-two MAAs identified, only two drug:indication pairings have been subsequently re-appraised by NICE: BV(brentuximab vedotin):non-Hodgkin lymphoma (’recommended’) and pembrolizumab:relapsed or refractory classical Hodgkin lymphoma (’recommended’). Data from a retrospective questionnaire regarding the proportion of patients that received curative stem cell transplant (SCT) post-BV (from patients who received BV in the old CDF) were accepted to provide sufficient evidence on the post-BV SCT rate by NICE. Meanwhile, for pembrolizumab, long-term survival benefit was the key clinical uncertainty; the primary data collection source was updated phase III randomized controlled trial data. At re-appraisal no reference was made to the observational data component; more mature survival data reduced uncertainty over survival benefits and were sufficient to support a positive NICE recommendation.

Of the twenty-two MAAs to date, only two drugs have been re-appraised thus far, with both receiving positive NICE recommendations. Observational data were successfully used to address key clinical uncertainties regarding subsequent real-world treatment patterns for BV, but observational data were not referred to in the NICE recommendation for pembrolizumab. The re-appraisal of more drugs in the future will clarify the importance being placed on observational data collection requested by NICE for existing MAAs.

The Early Access to Medicines Scheme (EAMS) aims to provide access to medicines prior to market authorization for patients with severe, life-threatening diseases who do not have adequate treatment options. An EAMS designation enables the potential collection of United Kingdom-specific real world evidence (RWE) prior to health technology assessment (HTA) by the National Institute for Health and Care Excellence (NICE). This research evaluates whether RWE is being gathered through the EAMS and utilized to support HTA submissions.

All EAMS designations as of 7 November 2018 were identified from the Medicines and Healthcare products Regulatory Agency website. For products with final NICE guidance, all publicly-available NICE documentation was reviewed.

Sixteen product and indication pairings with an EAMS designation were identified, with 12 having received final NICE guidance (11 were recommended, 3 were recommended for temporary reimbursement via the Cancer Drugs Fund, and 2 were not recommended). Of the 11 recommended products, seven had references to the number of patients or sites with product access through the EAMS, but only one (dupilumab for atopic dermatitis) had detailed data collected during the EAMS period. The manufacturer of dupilumab reported baseline demographics and disease characteristics from a cohort of 35 patients treated under the EAMS to inform the generalizability of trial populations for clinical practice. Follow-up results from this cohort demonstrated that real-world data on dupilumab effectiveness was comparable with the clinical trial data, despite a higher proportion of patients in the real-world cohort receiving immunosuppressant therapy, which makes improvements in efficacy harder to achieve. The committee also noted that the RWE presented supported the understanding of dupilumab's long-term clinical effectiveness and informed assumptions for the economic model.

To date, the majority of products receiving an EAMS designation have not presented RWE at NICE reappraisal. The case of dupilumab illustrated how RWE collected through the EAMS can be used to reduce uncertainty around how clinical trial data can be translated into clinical practice. In the future, RWE may increasingly be used to help inform NICE decisions.

The Cancer Drugs Fund (CDF) was set up in 2011 in England to enable patients to access oncology therapies that are not routinely publicly funded. In April 2016, the CDF became a temporary reimbursement fund under the remit of the National Institute for Health and Care Excellence (NICE) with the aim of collecting observational data to inform subsequent technology appraisals. This study aims to evaluate how the reformed CDF has been utilized in the 18 months since this reform.

NICE Final Appraisal Determinations for Single Technology Appraisals of oncology drugs from (29 July 2016 to 24 November 2017) were identified and key data extracted.

Seventy-four oncology drug:indication appraisals were identified, 54 (73 percent) were recommended/optimized, 10 (14 percent) were not recommended and 10 drug:indication pairings (14 percent: osimertinib, brentuximab vedotin, pembrolizumab, olaratumab, obinutuzumab, venetoclax, nivolumab [3 indications], and ibrutinib) were referred to the CDF. For most, the greatest uncertainty in their cost-effectiveness analyses related to their survival benefits, intended to primarily be resolved through subsequent clinical trial readouts. However, for venetoclax, ibrutinib and brentuximab, the main areas of uncertainty (relating to comparative survival benefit, pre-progression mortality, and rate of subsequent stem cell transplants, respectively) are expected to be resolved primarily through observational data collected under the CDF.

The newly reformed CDF has been utilized in a minority of cases. Typically, the CDF acts as a temporary access mechanism for treatments that receive market authorization based on early/single-arm trial data until longer-term and/or Phase III data are available. However, venetoclax, brentuximab, and ibrutinib demonstrate how the CDF may address significant areas of uncertainty through the collection of uncontrolled observational data. For venetoclax, with only single-arm supportive clinical trial data, observational data of this intervention and appropriate comparator are to be collected, providing a potential case study of how to appropriately manage reimbursement in the face of significant clinical uncertainty.

In recent years, the National Institute for Health and Care Excellence (NICE) has increasingly agreed to reimburse innovative products with high levels of uncertainty as part of managed access agreements (MAAs) while new data are collected; namely, this has occurred through the new Cancer Drugs Fund (CDF) and highly specialized technology (HST) appraisal pathway. This research aimed to provide a review of ongoing data collection arrangements as part of MAAs agreed with NICE.

We reviewed all current MAAs entered into between the National Health Service (NHS) England and manufacturers as of 24 November 2017 and extracted relevant information related to the data collection arrangements.

Thirteen MAAs were identified (10 through the CDF; 3 through HST). All MAAs involved an observational data collection agreement. The source of observational data collection was existing NHS databases (11 MAAs: 85 percent), existing independent registries (1 MMA: 8 percent [ataluren]); bespoke MAA registry maintained by manufacturer (1 MAA: 8 percent [asfotase alfa]), and registries developed as a requirement for regulatory approval and maintained by the manufacturer (1 MAA: 8 percent [elosulfase alfa]). Only 4 MAAs (asfotase alfa, ataluren, elosulfase alfa, and venetoclax) had observational data collection as the sole basis of the data collection agreement. The other 9 MAAs (69 percent; all from the CDF) also required on-going data collection from clinical trials as a key component of the data collection agreement.

This research shows that current MAAs have predominantly utilized either ongoing data collection (e.g. from RCTs) or existing registries to date for which limited additional set-up administration and costs would be required. However, NICE plan to increase the use of MAAs, with ongoing NICE consultation for changes in the appraisal process to expand MAAs to include all indications. In future, manufacturers will have more opportunities to explore and leverage innovative and bespoke MAAs to help achieve access.

Individuals who were born very preterm have higher rates of psychiatric diagnoses compared with term-born controls; however, it remains unclear whether they also display increased sub-clinical psychiatric symptomatology. Hence, our objective was to utilize a dimensional approach to assess psychiatric symptomatology in adult life following very preterm birth.

We studied 152 adults who were born very preterm (before 33 weeks’ gestation; gestational range 24–32 weeks) and 96 term-born controls. Participants’ clinical profile was examined using the Comprehensive Assessment of At-Risk Mental States (CAARMS), a measure of sub-clinical symptomatology that yields seven subscales including general psychopathology, positive, negative, cognitive, behavioural, motor and emotional symptoms, in addition to a total psychopathology score. Intellectual abilities were examined using the Wechsler Abbreviated Scale of Intelligence.

Between-group differences on the CAARMS showed elevated symptomatology in very preterm participants compared with controls in positive, negative, cognitive and behavioural symptoms. Total psychopathology scores were significantly correlated with IQ in the very preterm group only. In order to examine the characteristics of participants’ clinical profile, a principal component analysis was conducted. This revealed two components, one reflecting a non-specific psychopathology dimension, and the other indicating a variance in symptomatology along a positive-to-negative symptom axis. K-means (k = 4) were used to further separate the study sample into clusters. Very preterm adults were more likely to belong to a high non-specific psychopathology cluster compared with controls.

Very preterm individuals demonstrated elevated psychopathology compared with full-term controls. Their psychiatric risk was characterized by a non-specific clinical profile and was associated with lower IQ.