Correction to: Will the reformed Cancer Drugs Fund address the most common types of uncertainty? An analysis of NICE cancer drug appraisals.

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Will the reformed Cancer Drugs Fund address the most common types of uncertainty? An analysis of NICE cancer drug appraisals.

BACKGROUND: One of the functions of the reformed Cancer Drugs Fund in England is as a managed access fund, providing conditional funding for cancer drugs where there is uncertainty in the economic case, and where that uncertainty can be addressed by data collection during two years' use in the NHS. Our study characterises likely sources of such uncertainty, through a review of recent NICE Technology Appraisals. METHODS: Discussions of uncertainty in NICE Appraisal Committees were extracted from published Single Technology Appraisals of cancer drugs, 2014-2016, and categorised inductively. The location of the comments within the structured Appraisal document was used as a proxy for the degree of concern shown by the Committee. RESULTS: Twenty-nine appraisals were analysed, of which 23 (79%) were recommended for funding. Six main sources of uncertainty were identified. Immaturity of survival data, and issues relating to comparators, were common sources of uncertainty regardless of degree of concern. Uncertainties relating to quality of life, and the patient population in the trial, were discussed frequently but rarely occurred in the more uncertain appraisals. Concerns with trial design, and cost uncertainty, were less common, but a high proportion contributed to the most uncertain appraisals. Funding decisions were not driven by uncertainty in the evidence base, but by the expected cost per QALY relative to acceptance thresholds, and the resultant level of uncertainty in the decision. CONCLUSIONS: The reformed CDF is an improvement on its predecessor. However the main types of uncertainty seen in recent cancer appraisals will not readily be resolved solely by 2 years' RWD collection in the reformed CDF; where there are no ongoing trials to provide longer-term data, randomised trials rather than RWD may be needed to fully resolve questions of relative efficacy. Other types of uncertainty, and concerns with generalisability, may be more amenable to the RWD approach, and it is these that we expect to be the focus of data collection arrangements in the reformed CDF.

What Aspects of Illness Influence Public Preferences for Healthcare Priority Setting? A Discrete Choice Experiment in the UK.

BACKGROUND: Decisions on funding new healthcare technologies assume that all health improvements are valued equally. However, public reaction to health technology assessment (HTA) decisions suggests there are health attributes that matter deeply to them but are not currently accounted for in the assessment process. We aimed to determine the relative importance of attributes of illness that influence the value placed on alleviating that illness. METHOD: We conducted a discrete choice experiment survey that presented general public respondents with 15 funding decisions between hypothetical health conditions. The conditions were defined by five attributes that characterise serious illnesses, plus the health gain from treatment. Respondent preferences were modelled using conditional logistic regression and latent class analysis. RESULTS: 905 members of the UK public completed the survey in November 2017. Respondents generally preferred to provide treatments for conditions with 'better' characteristics. The exception was treatment availability, where respondents preferred to provide treatments for conditions where there is no current treatment, and were prepared to accept lower overall health gain to do so. A subgroup of respondents preferred to prioritise 'worse' health states. CONCLUSION: This study suggests a preference among the UK public for treating an unmet need; however, it does not suggest a preference for prioritising other distressing aspects of health conditions, such as limited life expectancy, or where patients are reliant on care. Our results are not consistent with the features currently prioritised in UK HTA processes, and the preference heterogeneity we identify presents a major challenge for developing broadly acceptable policy.

The Life Sciences Translational Challenge: The European Perspective.

In recent years, concern has been growing that traditional research and development models in the life sciences are unsustainable. Productivity, especially in pharmaceuticals, has plummeted, and too many of the products emerging from increasingly lengthy and costly clinical development offer marginal benefit to patients. Although the phenomenon is global, there are specific and important features of European life sciences that impede the translation of an ever more penetrating understanding of biology into effective treatments. This article analyzes these issues in the context of European biopharmaceutical innovation, describes the actions that Europe is already taking, and suggests what more needs to be done.

Realising the potential of adaptive development of medicines.

The recent launch of a pilot scheme for 'adaptive licensing' by the European Medicines Agency could spell a new era in drug development. Rather than focusing on the purely regulatory aspect of the system, the proposals challenge several aspects of existing development processes, including the conventional roles of sponsor, regulatory and reimbursement agencies, payers and patients. They also exploit a number of scientific advances not available when the existing development path was laid out. Like all other innovations the new model of adaptive development also carries significant challenges, in areas as diverse as clinical management, economics, intellectual property, ethics and public communications. This paper outlines these changes to thinking, summarizes the benefits the model offers and proposes how some of the challenges should be met. The perspectives in the paper are drawn from the authors' own involvement with this European project and are informed by discussions at several workshops and conferences held over recent months.

Enabling consistency in pluripotent stem cell-derived products for research and development and clinical applications through material standards.

There is a need for physical standards (reference materials) to ensure both reproducibility and consistency in the production of somatic cell types from human pluripotent stem cell (hPSC) sources. We have outlined the need for reference materials (RMs) in relation to the unique properties and concerns surrounding hPSC-derived products and suggest in-house approaches to RM generation relevant to basic research, drug screening, and therapeutic applications. hPSCs have an unparalleled potential as a source of somatic cells for drug screening, disease modeling, and therapeutic application. Undefined variation and product variability after differentiation to the lineage or cell type of interest impede efficient translation and can obscure the evaluation of clinical safety and efficacy. Moreover, in the absence of a consistent population, data generated from in vitro studies could be unreliable and irreproducible. Efforts to devise approaches and tools that facilitate improved consistency of hPSC-derived products, both as development tools and therapeutic products, will aid translation. Standards exist in both written and physical form; however, because many unknown factors persist in the field, premature written standards could inhibit rather than promote innovation and translation. We focused on the derivation of physical standard RMs. We outline the need for RMs and assess the approaches to in-house RM generation for hPSC-derived products, a critical tool for the analysis and control of product variation that can be applied by researchers and developers. We then explore potential routes for the generation of RMs, including both cellular and noncellular materials and novel methods that might provide valuable tools to measure and account for variation. Multiparametric techniques to identify "signatures" for therapeutically relevant cell types, such as neurons and cardiomyocytes that can be derived from hPSCs, would be of significant utility, although physical RMs will be required for clinical purposes.

Quantitative assessment of barriers to the clinical development and adoption of cellular therapies: A pilot study.

There has been a large increase in basic science activity in cell therapy and a growing portfolio of cell therapy trials. However, the number of industry products available for widespread clinical use does not match this magnitude of activity. We hypothesize that the paucity of engagement with the clinical community is a key contributor to the lack of commercially successful cell therapy products. To investigate this, we launched a pilot study to survey clinicians from five specialities and to determine what they believe to be the most significant barriers to cellular therapy clinical development and adoption. Our study shows that the main concerns among this group are cost-effectiveness, efficacy, reimbursement, and regulation. Addressing these concerns can best be achieved by ensuring that future clinical trials are conducted to adequately answer the questions of both regulators and the broader clinical community.

The implementation of novel collaborative structures for the identification and resolution of barriers to pluripotent stem cell translation.

Increased global connectivity has catalyzed technological development in almost all industries, in part through the facilitation of novel collaborative structures. Notably, open innovation and crowd-sourcing-of expertise and/or funding-has tremendous potential to increase the efficiency with which biomedical ecosystems interact to deliver safe, efficacious and affordable therapies to patients. Consequently, such practices offer tremendous potential in advancing development of cellular therapies. In this vein, the CASMI Translational Stem Cell Consortium (CTSCC) was formed to unite global thought-leaders, producing academically rigorous and commercially practicable solutions to a range of challenges in pluripotent stem cell translation. Critically, the CTSCC research agenda is defined through continuous consultation with its international funding and research partners. Herein, initial findings for all research focus areas are presented to inform global product development strategies, and to stimulate continued industry interaction around biomanufacturing, strategic partnerships, standards, regulation and intellectual property and clinical adoption.