111 research outputs found

    Implementing universal and targeted policies for health equity: lessons from Australia

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    ePublished: 9 November 2021Background: Debate continues in public health on the roles of universal or targeted policies in providing equity of access to health- related goods or services, and thereby contributing to health equity. Research examining policy implementation can provide fresh insights on these issues. Methods: We synthesised findings across case studies of policy implementation in four policy areas of primary healthcare (PHC), telecommunications, Indigenous health and land use policy, which incorporated a variety of universal and targeted policy structures. We analysed findings according to three criteria of equity in access – availability, affordability and acceptability – and definitions of universal, proportionate-universal, targeted and residual policies, and devolved governance structures. Results: Our analysis showed that existing universal, proportionate-universal and targeted policies in an Australian context displayed strengths and weaknesses in addressing availability, affordability and acceptability dimensions of equity in access. Conclusion: While residualist policies are unfavourable to equity of access, other forms of targeting as well as universal and proportionate-universal structure have the potential to be combined in context-specific ways favourable to equity of access to health-related goods and services. To optimise benefits, policies should address equity of access in the three dimensions of availability, affordability and acceptability. Devolved governance structures have the potential to augment equity benefits of either universal or targeted policies.Matthew Fisher, Patrick Harris, Toby Freeman, Tamara Mackean, Emma George, Sharon Friel, Fran Bau

    Health technology reassessment: the art of the possible

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    BACKGROUND: Health technology reassessment (HTR) is "a structured, evidence-based assessment of the clinical, social, ethical, and economic effects of a technology currently used in the healthcare system, to inform optimal use of that technology in comparison to its alternatives." The purpose of this study is to describe the key themes in the context of current HTR activities and propose a way forward for this newly emerging field. METHODS: Data were gathered from a workshop held as part of the 2012 Canadian Agency for Drugs and Technology in Health (CADTH) symposium. The workshop consisted of two panel presentations followed by discussion; data gathered, including presentations and rich audience discussion transcripts, were analyzed for key themes emerging in the field of HTR using constant comparative analysis. RESULTS: The language chosen to describe HTR will set the tone for engagement. The identification of champions at multiple levels and political will are essential. Key lessons from international experience are: disinvestment is difficult, focus on clinical areas not specific technologies, identify clear goals of the HTR agenda. Six key themes were identified to move the HTR agenda forward: emphasize integration over segregation, focus on development of HTR methods and processes, processes are context-specific but lessons must be shared, build capacity in synergistic interdisciplinary fields, develop meaningful stakeholder engagement, strengthen postimplementation monitoring and evaluation. CONCLUSIONS: To move this field forward, we must continue to build on international experiences with a focus on developing novel methodological approaches to generating, incorporating, and implementing evidence into policy and practice.Gail MacKean, Tom Noseworthy, Adam G. Elshaug, Laura Leggett, Peter Littlejohns, Joan Berezanski and Fiona Clemen

    Integrated molecular characterisation of endometrioid ovarian carcinoma identifies opportunities for stratification

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    Endometrioid ovarian carcinoma (EnOC) is an under-investigated ovarian cancer type. Recent studies have described disease subtypes defined by genomics and hormone receptor expression patterns; here, we determine the relationship between these subtyping layers to define the molecular landscape of EnOC with high granularity and identify therapeutic vulnerabilities in high-risk cases. Whole exome sequencing data were integrated with progesterone and oestrogen receptor (PR and ER) expression-defined subtypes in 90 EnOC cases following robust pathological assessment, revealing dominant clinical and molecular features in the resulting integrated subtypes. We demonstrate significant correlation between subtyping approaches: PR-high (PR + /ER + , PR + /ER−) cases were predominantly CTNNB1-mutant (73.2% vs 18.4%, P < 0.001), while PR-low (PR−/ER + , PR−/ER−) cases displayed higher TP53 mutation frequency (38.8% vs 7.3%, P = 0.001), greater genomic complexity (P = 0.007) and more frequent copy number alterations (P = 0.001). PR-high EnOC patients experience favourable disease-specific survival independent of clinicopathological and genomic features (HR = 0.16, 95% CI 0.04–0.71). TP53 mutation further delineates the outcome of patients with PR-low tumours (HR = 2.56, 95% CI 1.14–5.75). A simple, routinely applicable, classification algorithm utilising immunohistochemistry for PR and p53 recapitulated these subtypes and their survival profiles. The genomic profile of high-risk EnOC subtypes suggests that inhibitors of the MAPK and PI3K-AKT pathways, alongside PARP inhibitors, represent promising candidate agents for improving patient survival. Patients with PR-low TP53-mutant EnOC have the greatest unmet clinical need, while PR-high tumours—which are typically CTNNB1-mutant and TP53 wild-type—experience excellent survival and may represent candidates for trials investigating de-escalation of adjuvant chemotherapy to agents such as endocrine therapy

    The National Lung Matrix Trial of personalized therapy in lung cancer

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    The majority of targeted therapies for non-small-cell lung cancer (NSCLC) are directed against oncogenic drivers that are more prevalent in patients with light exposure to tobacco smoke1,2,3. As this group represents around 20% of all patients with lung cancer, the discovery of stratified medicine options for tobacco-associated NSCLC is a high priority. Umbrella trials seek to streamline the investigation of genotype-based treatments by screening tumours for multiple genomic alterations and triaging patients to one of several genotype-matched therapeutic agents. Here we report the current outcomes of 19 drug–biomarker cohorts from the ongoing National Lung Matrix Trial, the largest umbrella trial in NSCLC. We use next-generation sequencing to match patients to appropriate targeted therapies on the basis of their tumour genotype. The Bayesian trial design enables outcome data from open cohorts that are still recruiting to be reported alongside data from closed cohorts. Of the 5,467 patients that were screened, 2,007 were molecularly eligible for entry into the trial, and 302 entered the trial to receive genotype-matched therapy—including 14 that re-registered to the trial for a sequential trial drug. Despite pre-clinical data supporting the drug–biomarker combinations, current evidence shows that a limited number of combinations demonstrate clinically relevant benefits, which remain concentrated in patients with lung cancers that are associated with minimal exposure to tobacco smoke

    Phase I study of intermittent and chronomodulated oral therapy with capecitabine in patients with advanced and/or metastatic cancer

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    BACKGROUND: The combination of capecitabine and gemcitabine at Fixed Dose Rate (FDR) has been demonstrated to be well tolerated, with apparent efficacy in patients with advanced cancers. FDR gemcitabine infusion leads to enhanced intracellular accumulation of drug and possible augmented clinical effect. The goals of this phase I study were to determine the maximum-tolerated dose (MTD) of chronomodulated capecitabine in patients with advanced cancer and to describe the dose-limiting toxicities (DLT), the safety profile of this way of administration. METHODS: Patients with advanced solid tumours who had failed to response to standard therapy or for whom no standard therapy was available were elegible for this study. Capecitabine was administered orally according to following schedule: 1/4 of dose at 8:00 a.m.; 1/4 of dose at 6:00 p.m. and 1/2 of dose at 11:00 p.m. each day for 14 consecutive days, followed by a 7-day rest period. RESULTS: All 27 patients enrolled onto the study were assessable for toxicity. The most common toxicities during the first two cycles of chemotherapy were fatigue, diarrhoea and hand foot syndrome (HFS). Only one out of the nine patients treated at capecitabine dose of 2,750 mg/m(2 )met protocol-specified DLT criteria (fatigue grade 4). However, at these doses the majority of cycles of therapy were delivered without dose reduction or delay. No other episodes of DLT were observed at the same dose steps and at the lower dose steps of capecitabine (1,500/1,750/2,000/2,250/2,500 mg/m(2)). The dose of 2,750 mg/m(2 )is recommended for further study. Tumor responses were observed in patients with metastatic breast and colorectal cancer. CONCLUSION: High doses of chronomodulated capecitabine can be administered with acceptable toxicity. The evidence of antitumor activity deserves further investigation in phase II combination chemotherapy studies

    Defining the road map to a UK national lung cancer screening programme

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    Lung cancer screening with low-dose CT was recommended by the UK National Screening Committee (UKNSC) in September, 2022, on the basis of data from trials showing a reduction in lung cancer mortality. These trials provide sufficient evidence to show clinical efficacy, but further work is needed to prove deliverability in preparation for a national roll-out of the first major targeted screening programme. The UK has been world leading in addressing logistical issues with lung cancer screening through clinical trials, implementation pilots, and the National Health Service (NHS) England Targeted Lung Health Check Programme. In this Policy Review, we describe the consensus reached by a multiprofessional group of experts in lung cancer screening on the key requirements and priorities for effective implementation of a programme. We summarise the output from a round-table meeting of clinicians, behavioural scientists, stakeholder organisations, and representatives from NHS England, the UKNSC, and the four UK nations. This Policy Review will be an important tool in the ongoing expansion and evolution of an already successful programme, and provides a summary of UK expert opinion for consideration by those organising and delivering lung cancer screenings in other countries
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