Evaluating clinical decision support software (CDSS): challenges for robust evidence generation.

OBJECTIVES: Computerized clinical decision support software (CDSS) are digital health technologies that have been traditionally categorized as medical devices. However, the evaluation frameworks for traditional medical devices are not well adapted to assess the value and safety of CDSS. In this study, we identified a range of challenges associated with CDSS evaluation as a medical device and investigated whether and how CDSS are evaluated in Australia. METHODS: Using a qualitative approach, we interviewed 11 professionals involved in the implementation and evaluation of digital health technologies at national and regional levels. Data were thematically analyzed using both data-driven (inductive) and theory-based (deductive) approaches. RESULTS: Our results suggest that current CDSS evaluations have an overly narrow perspective on the risks and benefits of CDSS due to an inability to capture the impact of the technology on the sociotechnical environment. By adopting a static view of the CDSS, these evaluation frameworks are unable to discern how rapidly evolving technologies and a dynamic clinical environment can impact CDSS performance. After software upgrades, CDSS can transition from providing information to specifying diagnoses and treatments. Therefore, it is not clear how CDSS can be monitored continuously when changes in the software can directly affect patient safety. CONCLUSION: Our findings emphasize the importance of taking a living health technology assessment approach to the evaluation of digital health technologies that evolve rapidly. There is a role for observational (real-world) evidence to understand the impact of changes to the technology and the sociotechnical environment on CDSS performance.

Establishing a clinical ethics support service: lessons from the first 18 months of a new Australian service - a case study.

BACKGROUND: Although the importance of clinical ethics in contemporary clinical environments is established, development of formal clinical ethics services in the Australia health system has, to date, been ad hoc. This study was designed to systematically follow and reflect upon the first 18 months of activity by a newly established service, to examine key barriers and facilitators to establishing a new service in an Australian hospital setting. METHODS: HOW THE STUDY WAS PERFORMED AND STATISTICAL TESTS USED: A qualitative case study approach was utilised. The study gathered and analysed data using observations of service committee meetings, document analysis of agendas and minutes, and semi-structured interviews with committee members to generate semantic themes. By interpreting the thematic findings in reference to national capacity building resources, this study also aimed to provide practice-based reflections for other health agencies. RESULTS: THE MAIN FINDINGS: An overarching theme identified in the data was a strong commitment to supporting clinicians facing difficult patient care decisions and navigating difficult discussions with patients and families. Another key theme was the role of the new clinical ethics support service in providing clinicians with a pathway to raise system-wide issues with the organisation Executive. While there was strong clinical engagement, consumer and community participation remained a challenge, as did unresolved governance issues and a need for clearer policy relationship between the service and the organisation. Considering these themes in relation to the national capacity building resources, the study identifies three areas likely to require ongoing development and negotiation. These are: the role of the clinical ethics support service as a link between the workforce and the Executive; the incorporation of consumers and patients; and ethical reasoning. To improve the effectiveness of the service, it is necessary to increase clarity on the service's role at the governance and policy level, as well as develop strategies for engaging consumers, patients and families. Finally, the capacity of the service to reflect on complex cases may be enhanced through explicit discussions of various different ethical frameworks and ways of deliberating.

Design and validation of a chart-based measure of the limits of spatial contrast sensitivity.

PURPOSE: Current chart-based tests of spatial contrast sensitivity (SCS) with fixed or narrow frequency ranges (≤18 cycles/°) cannot characterise the limits of spatial contrast vision. Here we present the design and validation of a chart-based measure of the spatial contrast envelope. METHODS: Following the principles of the standard visual acuity (Bailey-Lovie) and contrast sensitivity (Pelli-Robson) charts, a combined spatial-contrast and visual acuity chart was designed using a language-independent triangular symbol for a four-alternative forced-choice procedure plus chart rotation. Symbol frequencies ranged between 0.38 and 60 cycles/° spaced along 10 radial axes (0.55%-100% contrast). The chart was validated with reference to the Bailey-Lovie and Pelli-Robson charts; its reliability and sensitivity to changes in illumination, simulated cataract and blur was evaluated in healthy adults. RESULTS: The photopic SCS function could be measured in 5.5 ± 0.5 min; thresholding around the spatial contrast resolution limit reduced completion times to ~2 min. There was good agreement with high-contrast visual acuity (difference = 0.08 ± 0.02 logMAR) and contrast-sensitivity at 1.5 cycles/° (0.13 ± 0.06 logCS). Test-retest reliability was excellent at all spatial frequencies (ICC = 0.99). Mesopic illumination or simulated cataract caused a generalised SCS loss; myopic blur reduced high-frequency sensitivity. Spatial contrast sensitivity was independent of radial axis orientation (cardinal or oblique). CONCLUSIONS: The chart provides a time-efficient, reliable and inexpensive measure of SCS with applications in research and clinic for detecting subtle deficits in early stages of ocular and neurological conditions that often manifest at higher frequencies. It is sensitive to vision changes occurring in dim lighting and with simulated cataract and blur. The chart is available open-access for self-printing; contrast variation in print can be controlled through user calibration and/or establishing normative SCS functions using the theoretical values.

Neglected impacts of patient decision-making associated with genetic testing.

We highlight non-health-related impacts associated with genetic testing (GT) and knowing one's genetic status so that health technology assessment (HTA) analysts and HTA audiences may more appropriately consider the pros and cons of GT. Whereas health-related impacts of GT (e.g., increased healthy behaviors and avoidance of harms of unnecessary treatment) are frequently assessed in HTA, some non-health-related impacts are less often considered and are more difficult to measure. This presents a challenge for accurately assessing whether a genetic test should be funded. In health systems where HTA understandably places emphasis on measurable clinical outcomes, there is a risk of creating a GT culture that is pro-testing without sufficient recognition of the burdens of GT. There is also a risk of not funding a genetic test that provides little clinical benefit but nonetheless may be seen by some as autonomy enhancing. The recent development of expanded HTA frameworks that include ethics analyses helps to address this gap in the evidence and bring awareness to non-health-related impacts of GT. The HTA analyst should be aware of these impacts, choose appropriate frameworks for assessing genetic tests, and use methods for evaluating impacts. A new reporting tool presented here may assist in such evaluations.

Prenatal genetic testing for cystic fibrosis: a systematic review of clinical effectiveness and an ethics review.

PURPOSE: We aimed to assess the clinical value of prenatal testing for cystic fibrosis (CF) and whether ethical considerations would affect endpoint selection. METHODS: To determine effectiveness, we conducted a systematic literature review whose protocol outlined search strategies across eight databases, study inclusion criteria, and prespecified literature screening, data extraction, and synthesis processes. We conducted a scoping search on ethical considerations. RESULTS: The genetic test showed good diagnostic performance. A change in clinical management was observed: termination of pregnancy (TOP) occurred in most cases where two pathogenic variants were identified in a fetus of carrier parents (158/167; 94.6%). The TOP rate was lower in pregnancies where CF was diagnosed after fetal echogenic bowel detection (~65%). TOP and caring for a child with CF were both associated with poor short-term parental psychological outcomes. Ethical analyses indicated that informed decisions should have been the main endpoint, rather than CF-affected births prevented. CONCLUSION: CF testing leads to fewer CF-affected births. It is difficult to assess whether this means the test is valuable, since patients may not value TOP primarily in terms of maternal or fetal health outcomes, psychological or otherwise. The value of testing should arguably be measured in terms of improving patient autonomy rather than health.

Assessing the quality of health research from an Indigenous perspective: the Aboriginal and Torres Strait Islander quality appraisal tool.

BACKGROUND: The lack of attention to Indigenous epistemologies and, more broadly, Indigenous values in primary research, is mirrored in the standardised critical appraisal tools used to guide evidence-based practice and systematic reviews and meta-syntheses. These critical appraisal tools offer no guidance on how validity or contextual relevance should be assessed for Indigenous populations and cultural contexts. Failure to tailor the research questions, design, analysis, dissemination and knowledge translation to capture understandings that are specific to Indigenous peoples results in research of limited acceptability and benefit and potentially harms Indigenous peoples. A specific Aboriginal and Torres Strait Islander Quality Appraisal Tool is needed to address this gap. METHOD: The Aboriginal and Torres Strait Islander Quality Appraisal Tool (QAT) was developed using a modified Nominal Group and Delphi Techniques and the tool's validity, reliability, and feasibility were assessed over three stages of independent piloting. National and international research guidelines were used as points of reference. Piloting of the Aboriginal and Torres Strait Islander QAT with Aboriginal and Torres Strait Islander and non-Indigenous experts led to refinement of the tool. RESULTS: The Aboriginal and Torres Strait Islander QAT consists of 14 questions that assess the quality of health research from an Aboriginal and Torres Strait Islander perspective. The questions encompass setting appropriate research questions; community engagement and consultation; research leadership and governance; community protocols; intellectual and cultural property rights; the collection and management of research material; Indigenous research paradigms; a strength-based approach to research; the translation of findings into policy and practice; benefits to participants and communities involved; and capacity strengthening and two-way learning. Outcomes from the assessment of the tool's validity, reliability, and feasibility were overall positive. CONCLUSION: This is the first tool to appraise research quality from the perspective of Indigenous peoples. Through the uptake of the Aboriginal and Torres Strait Islander QAT we hope to improve the quality and transparency of research with Aboriginal and Torres Strait Islander peoples, with the potential for greater improvements in Aboriginal and Torres Strait Islander health and wellbeing.

The rationale and design of public involvement in health-funding decision making: focus groups with the Canadian public.

BACKGROUND: Worldwide, governments employ health technology assessment (HTA) in healthcare funding decision making. Requests to include public perspectives in this are increasing, with the idea being that the public can identify social values to guide policy development, increasing the transparency and accountability of government decision making. OBJECTIVE: To understand the perspectives of the Canadian public on the rationale and design of public involvement in HTA. DESIGN: A demographically representative sample of residents of a Canadian province was selected to take part in two sets of two focus groups (sixteen people for the first set and twenty for the second set). RESULTS: Participants were suspicious of the interests driving various stakeholders involved in HTA. They saw the public as uniquely impartial though also lacking knowledge about health technologies. Participants were also suspicious of personal biases and commended mechanisms to reduce their impact. Participants suggested various involvement methods, such as focus groups, citizens' juries and surveys, noting advantages and disadvantages belonging to each and commending a combination. DISCUSSION AND CONCLUSIONS: We identified a lack of public understanding of how decisions are made and distrust concerning whose interests and values are being considered. Public involvement was seen as a way of providing information to the public and ascertaining their views and values. Participants suggested that public involvement should employ a mixed-methods strategy to support informed debate and participation of a large number of people.

An Ethical Analysis of Coverage With Evidence Development.

Sometimes a government or other payer is called on to fund a new health technology even when the evidence leaves a lot of uncertainty. One option is for the payer to provisionally fund the technology and reduce uncertainty by developing evidence. This is called coverage with evidence development (CED). Only-in-research CED, when the payer funds the technology only for patients who participate in the evidence development, raises the sharpest ethical questions. Is the patient coerced or induced into participating? If so, under what circumstances, if any, is this ethically justified? Building on work by Miller and Pearson, we argue that patients have a right to funding for a technology only when the payer can be confident that the technology provides reasonable value for money. Technologies are candidates for CED precisely because serious questions remain about value for money, and therefore patients have no right to technologies under a CED arrangement. This is why CED induces rather than coerces. The separate question of whether the inducement is ethically justified remains. We argue that CED does pose risks to patients, and the worse these risks are, the harder it is to justify the inducement. Finally, we propose conditions under which the inducement could be ethically justified and means of avoiding inducement altogether. We draw on the Australian context, and so our conclusions apply most directly to comparable contexts, where the payer is a government that provides universal coverage with a regard for cost-effectiveness that is prominent and fairly clearly defined.

Constructions of alcohol consumption by non-problematised middle-aged drinkers: a qualitative systematic review.

BACKGROUND: Current research into alcohol consumption focuses predominantly on problematic drinkers and populations considered likely to engage in risky behaviours. Middle-aged drinkers are an under-researched group, despite emerging evidence that their regular drinking patterns may carry some risk. METHODS: We searched Scopus, Ovid Medline, and Ovid PsycInfo for peer-reviewed, English-language publications appearing prior to 31 December 2015 and relating to the construction of alcohol consumption by middle-aged non-problematised drinkers. Thirteen papers were included in our thematic analysis. RESULTS: Middle-aged non-problematised drinkers constructed their drinking practices by creating a narrative of normative drinking via discourses of gender, identity, play, and learning to drink. They also used drinking norms to construct their gender and identity. Health was not identified as a significant consideration for the population of interest when constructing alcohol consumption, except where drinking behaviours were likely to harm another. CONCLUSIONS: These results suggest that public health campaigns aimed at reducing alcohol consumption may be more effective if they focus on unacceptable drinking behaviours instead of personal health outcomes.

The development of funding recommendations for health technologies at the state level: A South Australian case study.

OBJECTIVES: State governments often face capped budgets that can restrict expenditure on health technologies and their evaluation, yet many technologies are introduced to practice through state-funded institutions such as hospitals, rather than through national evaluation mechanisms. This research aimed to identify the criteria, evidence, and standards used by South Australian committee members to recommend funding for high-cost health technologies. METHODS: We undertook 8 semi-structured interviews and 2 meeting observations with members of state-wide committees that have a mandate to consider the safety, effectiveness, and cost-effectiveness of high-cost health technologies. RESULTS: Safety and effectiveness were fundamental criteria for decision makers, who were also concerned with increasing consistency in care and equitable access to technologies. Committee members often consider evidence that is limited in quantity and quality; however, they perceive evaluations to be rigorous and sufficient for decision making. Precise standards for safety, effective, and cost-effectiveness could not be identified. CONCLUSIONS: Consideration of new technologies at the state level is grounded in the desire to improve health outcomes and equity of access for patients. High quality evidence is often limited. The impact funding decisions have on population health is unclear due to limited use of cost-effectiveness analysis and unclear cost-effectiveness standards.

Involving patients in health technology funding decisions: stakeholder perspectives on processes used in Australia.

BACKGROUND: Governments use a variety of processes to incorporate public perspectives into policymaking, but few studies have evaluated these processes from participants' point of view. OBJECTIVE: The objective of this study was twofold: to understand the perspectives of selected stakeholders with regard to involvement processes used by Australian Advisory Committees to engage the public and patients; and to identify barriers and facilitators to participation. DESIGN: Twelve semi-structured interviews were conducted with representatives of different stakeholder groups involved in health technology funding decisions in Australia. Data were collected and analysed using a theoretical framework created by Rowe and Frewer, but adapted to more fully acknowledge issues of power and influence. RESULTS: Stakeholder groups disagreed as to what constitutes effective and inclusive patient involvement. Barriers reported by interviewees included poor communication, a lack of transparency, unworkable deadlines, and inadequate representativeness. Also described were problems associated with defining the task for patients and their advocates and with the timing of patient input in the decision-making process. Interviewees suggested that patient participation could be improved by increasing the number of patient organizations engaged in processes and including those organizations at different stages of decision making, especially earlier. CONCLUSIONS: The different evaluations made by stakeholder groups appear to be underpinned by contrasting conceptions of public involvement and its value, in line with Graham Martin's work which distinguishes between 'technocratic' and 'democratic' public involvement. Understanding stakeholders' perspectives and the contrasting conceptions of public involvement could foster future agreement on which processes should be used to involve the public in decision making.

Justice and Surgical Innovation: The Case of Robotic Prostatectomy.

Surgical innovation promises improvements in healthcare, but it also raises ethical issues including risks of harm to patients, conflicts of interest and increased injustice in access to health care. In this article, we focus on risks of injustice, and use a case study of robotic prostatectomy to identify features of surgical innovation that risk introducing or exacerbating injustices. Interpreting justice as encompassing matters of both efficiency and equity, we first examine questions relating to government decisions about whether to publicly fund access to innovative treatments. Here the case of robotic prostatectomy exemplifies the difficulty of accommodating healthcare priorities such as improving the health of marginalized groups. It also illustrates challenges with estimating the likely long-term costs and benefits of a new intervention, the difficulty of comparing outcomes of an innovative treatment to those of established treatments, and the further complexity associated with patient and surgeon preferences. Once the decision has been made to fund a new procedure, separate issues of justice arise at the level of providing care to individual patients. Here, the case of robotic prostatectomy exemplifies how features of surgical innovation, such as surgeon learning curves and the need for an adequate volume of cases at a treatment centre, can exacerbate injustices associated with treatment cost and the logistics of travelling for treatment. Drawing on our analysis, we conclude by making a number of recommendations for the just introduction of surgical innovations.

Why is Pain Still Under-Treated in the Emergency Department? Two New Hypotheses.

Across the world, pain is under-treated in emergency departments (EDs). We canvass the literature testifying to this problem, the reasons why this problem is so important, and then some of the main hypotheses that have been advanced in explanation of the problem. We then argue for the plausibility of two new hypotheses: pain's under-treatment in the ED is due partly to (1) an epistemic preference for signs over symptoms on the part of some practitioners, and (2) some ED practices that themselves worsen pain by increasing patients' anxiety and fear. Our argument includes the following logic. Some ED practitioners depart from formal guidance in basing their acute pain assessments on observable features rather than on patient reports of pain. This is potentially due to an epistemic preference for signs over symptoms which aims to circumvent intentional and/or unintentional misrepresentation on the part of patients. However, conducting pain assessments in line with this epistemic preference contributes to the under-treatment of pain in at least three respects, which we detail. Moreover, it may do little to help the practitioner circumvent any intentional misrepresentation on the part of the patient, as we explain. Second, we examine at least four ED practices that may be contributing to the under-treatment of pain by increasing patient anxiety and fear, which can worsen pain. These practices include failing to provide orienting information and partially objectifying patients so as to problem-solve along lines pre-established by modern medical science. We conclude by touching on some potential solutions for ED practice.

Competing Principles for Allocating Health Care Resources.

We clarify options for conceptualizing equity, or what we refer to as justice, in resource allocation. We do this by systematically differentiating, expounding, and then illustrating eight different substantive principles of justice. In doing this, we compare different meanings that can be attributed to "need" and "the capacity to benefit" (CTB). Our comparison is sharpened by two analytical tools. First, quantification helps to clarify the divergent consequences of allocations commended by competing principles. Second, a diagrammatic approach developed by economists Culyer and Wagstaff offers a visual and conceptual aid. Of the eight principles we illustrate, only two treat as relevant both a person's initial health state and a person's CTB per resource unit expended: (1) allocate resources so as to most closely equalize final health states and (2) allocate resources so as to equally restore health states to population norms. These allocative principles ought to be preferred to the alternatives if one deems relevant both a person's initial health state and a person's CTB per resource unit expended. Finally, we examine some possibilities for conceptualizing benefits as relative to how badly off someone is, extending Parfit's thought on Prioritarianism (a prioritizing of the worst off). Questions arise as to how much intervention effects accruing to the worse off count for more and how this changes with improving health. We explicate some recent efforts to answer these questions, including in Dutch and British government circles. These efforts can be viewed as efforts to operationalize need as an allocative principle. Each effort seeks to maximize in the aggregate quanta of effect that are differentially valued in favor of the worst off. In this respect, each effort constitutes one type of Prioritarianism, which Parfit failed to differentiate from other types.

Building workforce capacity for ethical reflection in health promotion: a practitioner's experience.

Health promotion does not have a code of ethics, although attempts have been made to assist practitioners in their understanding and application of ethical concepts. This article describes and analyses one such attempt, sustained from 2006 to 2014 in rural South Australia. The attempt comprised capacity-building activities that were informed by principles of organisational change management, especially the principle of creating champions. The article also presents a framework (largely comprising ethical questions) that may help practitioners as a prompt and guide to ethical reflection. The framework was developed to be as accessible as possible in light of the diverse educational backgrounds found in rural settings. Finally, the article highlights some philosophical dimensions to the framework and defends its role, proposing that ethical reflection is integral to good practice and never simply the province of theorists. The article does all this with a view to stimulating discussion on how to increase the frequency and quality of ethical reflection undertaken by health promotion practitioners.

Disinvestment policy and the public funding of assisted reproductive technologies: outcomes of deliberative engagements with three key stakeholder groups.

BACKGROUND: Measures to improve the quality and sustainability of healthcare practice and provision have become a policy concern. In addition, the involvement of stakeholders in health policy decision-making has been advocated, as complex questions arise around the structure of funding arrangements in a context of limited resources. Using a case study of assisted reproductive technologies (ART), deliberative engagements with a range of stakeholder groups were held on the topic of how best to structure the distribution of Australian public funding in this domain. METHODS: Deliberative engagements were carried out with groups of ART consumers, clinicians and community members. The forums were informed by a systematic review of ART treatment safety and effectiveness (focusing, in particular, on maternal age and number of treatment cycles), as well as by international policy comparisons, and ethical and cost analyses. Forum discussions were transcribed and subject to thematic analysis. RESULTS: Each forum demonstrated stakeholders' capacity to understand concepts of choice under resource scarcity and disinvestment, and to countenance options for ART funding not always aligned with their interests. Deliberations in each engagement identified concerns around 'equity' and 'patient responsibility', culminating in a broad preference for (potential) ART subsidy restrictions to be based upon individual factors rather than maternal age or number of treatment cycles. Community participants were open to restrictions based upon measures of body mass index (BMI) and smoking status, while consumers and clinicians saw support to improve these factors as part of an ART treatment program, as distinct from a funding criterion. All groups advocated continued patient co-payments, with measures in place to provide treatment access to those unable to pay (namely, equity of access). CONCLUSIONS: Deliberations yielded qualitative, socially-negotiated evidence required to inform ethical, accountable policy decisions in the specific area of ART and health care more broadly. Notably, reductionist, deterministic characterizations of stakeholder 'self-interest' proved unfounded as each group sought to prioritise universal values (in particular, 'equity' and 'responsibility') over specific, within-group concerns. Our results--from an emotive case study in ART--highlight that evidence-informed disinvestment decision-making is feasible, and potentially less controversial than often presumed.

Efficacy of biologically-directed daylight therapy on sleep and circadian rhythm in Parkinson's disease: a randomised, double-blind, parallel-group, active-controlled, phase 2 clinical trial.

Background: New non-pharmacological treatments for improving non-motor symptoms in Parkinson's disease (PD) are urgently needed. Previous light therapies for modifying sleep behaviour lacked standardised protocols and were not personalised for an individual patient chronotype. We aimed to assess the efficacy of a biologically-directed light therapy in PD that targets retinal inputs to the circadian system on sleep, as well as other non-motor and motor functions. Methods: In this randomised, double-blind, parallel-group, active-controlled trial at the Queensland University of Technology, Australia, participants with mild to moderate PD were computer randomised (1:1) to receive one of two light therapies that had the same photometric luminance and visual appearance to allow blinding of investigators and participants to the intervention. One of these biologically-directed lights matched natural daylight (Day Mel), which is known to stimulate melanopsin cells. The light therapy of the other treatment arm of the study, specifically supplemented the stimulation of retinal melanopsin cells (Enhanced Mel), targeting deficits to the circadian system. Both lights were administered 30 min per day over 4-weeks and personalised to an individual patient's chronotype, while monitoring environmental light exposure with actigraphy. Co-primary endpoints were a change from baseline in mean sleep macrostructure (polysomnography, PSG) and an endocrine biomarker of circadian phase (dim light melatonin secretion onset, DLMO) at weeks 4 and 6. Participants data were analysed using an intention to treat principle. All endpoints were evaluated by applying a mixed model analysis. The trial is registered with the Australian New Zealand Clinical Trials Registry, ACTRN12621000077864. Findings: Between February 4, 2021 and August 8, 2022, 144 participants with PD were consecutively screened, 60 enrolled and randomly assigned to a light intervention. There was no significant difference in co-primary outcomes between randomised groups overall or at any individual timepoint during follow-up. The mean (95% CI) for PSG, N3% was 24.15 (19.82-28.48) for Day Mel (n = 23) and 19.34 (15.20-23.47) for the Enhanced Mel group (n = 25) in week 4 (p = 0.12); and 21.13 (16.99-25.28) for Day Mel (n = 26) and 18.48 (14.34-22.62) for the Enhanced Mel group (n = 25) in week 6, (p = 0.37). The mean (95% CI) DLMO (decimal time) was 19.82 (19.20-20.44) for Day Mel (n = 22) and 19.44 (18.85-20.04) for the Enhanced Mel group (n = 24) in week 4 (p = 0.38); and 19.90 (19.27-20.53) for Day Mel (n = 23) and 19.04 (18.44-19.64) for the Enhanced Mel group (n = 25) in week 6 (p = 0.05). However, both the controlled daylight (Day Mel) and the enhanced melanopsin (Enhanced Mel) interventions demonstrated significant improvement in primary PSG sleep macrostructure. The restorative deep sleep phase (PSG, N3) significantly improved at week 6 in both groups [model-based mean difference to baseline (95% CI): -3.87 (-6.91 to -0.83), p = 0.04]. There was a phase-advance in DLMO in both groups which did not reach statistical significance between groups at any time-point. There were no safety concerns or severe adverse events related to the intervention. Interpretation: Both the controlled daylight and melanopsin booster light showed efficacy in improving measures of restorative deep sleep in people with mild to moderate PD. That there was no significant difference between the two intervention groups may be due to the early disease stage. The findings suggest that controlled indoor daylight that is personalised to the individuals' chronotype could be effective for improving sleep in early to moderate PD, and further studies evaluating controlled daylight interventions are now required utilising this standardised approach, including in advanced PD. Funding: The Michael J Fox Foundation for Parkinson's Research, Shake IT Up Australia, National Health and Medical Research Council, and Australian Research Council.

Melanoma follow up: time to generate the evidence.

Research is needed into current melanoma follow-up practices and their implications for patients and society. We highlight the need and suggest a way forward.

Challenges in the Evaluation of Emerging Highly Specialised Technologies: Is There a Role for Living HTA?

There is currently deep uncertainty about the clinical benefits and cost effectiveness of highly specialised technologies (HSTs), like gene and cell therapies. These treatments are novel, typically have high upfront costs, the patient populations are small and heterogenous, there is minimal information on their long-term safety and effectiveness, and data are limited and often of poor quality. With the increasing number of these technologies and their high cost burden on governments and health care providers, policy makers are currently walking a decision tightrope. On the one hand, an unfavourable funding decision could potentially limit patient access to life-saving treatments, while on the other, a favourable decision could result in unsustainable budget impacts and perhaps poorer patient health outcomes. Health technology assessment (HTA) is meant to determine the value of a health technology in order to promote an equitable, efficient, and high-quality health system. However, standard HTA processes have failed to mitigate the deep uncertainties associated with these technologies. In this paper, we propose a Living HTA framework to address these challenges. This framework includes a one-off process for making explicit the societal values associated with HSTs. These would inform the decision-making approach, data collection and the development of disease-specific reference models to be used by industry sponsors as the basis for their submissions for public funding. Coverage with an evidence development mechanism is also proposed by which data can be collected in real time to update the reference model on a rolling basis, thereby allowing re-assessment of the clinical and cost effectiveness of individual HSTs. The HTA would be 'live' until the results indicate there is sufficient certainty for the funding decision to be confirmed, the price changed or the funding removed.