Melbourne School of Population and Global Health - Research Publications
Permanent URI for this collection
Search Results
1 - 10 of 93
-
ItemNo Preview AvailableReal-world clinical outcomes and cost estimates of metastatic castration-resistant prostate cancer treatment: does sequencing of taxanes and androgen receptor-targeted agents matter?(TAYLOR & FRANCIS LTD, 2023-02-07)INTRODUCTION: Health economic outcomes of real-world treatment sequencing of androgen receptor-targeted agents (ARTA) and docetaxel (DOC) remain unclear. MATERIAL AND METHODS: Data from the electronic Castration-resistant Prostate cancer Australian Database (ePAD) were analyzed including median overall survival (mOS) and median time-to-treatment failure (mTTF). Mean total costs (mTC) and incremental cost-effectiveness ratios (ICER) of treatment sequences were estimated using the average sample method and Zhao and Tian estimator. RESULTS: Of 752 men, 441 received ARTA, 194 DOC, and 175 both sequentially. Of participants treated with both, first-line DOC followed by ARTA was the more common sequence (n = 125, 71%). mOS for first-line ARTA was 8.38 years (95% CI: 3.48, not-estimated) vs. 3.29 years (95% CI: 2.92, 4.02) for DOC. mTTF was 15.7 months (95% CI: 14.2, 23.7) for the ARTA-DOC sequence and 18.2 months (95% CI: 16.2, 23.2) for DOC-ARTA. In first-line, ARTA cost an additional $13,244 per mTTF month compared to DOC. In second-line, ARTA cost $6726 per mTTF month. The DOC-ARTA sequence saved $2139 per mTTF compared to ARTA-DOC, though not statistically significant. CONCLUSION: ICERs show ARTA had improved clinical benefit compared to DOC but at higher cost. There were no significant cost differences between combined sequences.
-
ItemNo Preview AvailableA systematic review of methodological considerations in time to diagnosis and treatment in colorectal cancer research(ELSEVIER SCI LTD, 2023-04)Research focusing on timely diagnosis and treatment of colorectal cancer is necessary to improve outcomes for people with cancer. Previous attempts to consolidate research on time to diagnosis and treatment have noted varied methodological approaches and quality, limiting the comparability of findings. This systematic review was conducted to comprehensively assess the scope of methodological issues in this field and provide recommendations for future research. Eligible articles had to assess the role of any interval up to treatment, on any outcome in colorectal cancer, in English, with no limits on publication time. Four databases were searched (Ovid Medline, EMBASE, EMCARE and PsycInfo). Papers were screened by two independent reviewers using a two-stage process of title and abstract followed by full text review. In total, 130 papers were included and had data extracted on specific methodological and statistical features. Several methodological problems were identified across the evidence base. Common issues included arbitrary categorisation of intervals (n = 107, 83%), no adjustment for potential confounders (n = 65, 50%), and lack of justification for included covariates where there was adjustment (n = 40 of 65 papers that performed an adjusted analysis, 62%). Many articles introduced epidemiological biases such as immortal time bias (n = 37 of 80 papers that used survival as an outcome, 46%) and confounding by indication (n = 73, 56%), as well as other biases arising from inclusion of factors outside of their temporal sequence. However, determination of the full extent of these problems was hampered by insufficient reporting. Recommendations include avoiding artificial categorisation of intervals, ensuring bias has not been introduced due to out-of-sequence use of key events and increased use of theoretical frameworks to detect and reduce bias. The development of reporting guidelines and domain-specific risk of bias tools may aid in ensuring future research can reliably contribute to recommendations regarding optimal timing and strengthen the evidence base.
-
ItemThe risk of contracting SARS-CoV-2 or developing COVID-19 for people with cancer: A systematic review of the early evidence(ELSEVIER SCI LTD, 2022-09)BACKGROUND: The early COVID-19 literature suggested that people with cancer may be more likely to be infected with SARS-CoV-2 or develop COVID-19 than people without cancer, due to increased health services contact and/or immunocompromise. While some studies were criticised due to small patient numbers and methodological limitations, they created or reinforced concerns of clinicians and people with cancer. These risks are also important in COVID-19 vaccine prioritisation decisions. We performed a systematic review to critically assess and summarise the early literature. METHODS AND FINDINGS: We conducted a systematic search of Medline/Embase/BioRxiv/MedRxiv/SSRN databases including peer-reviewed journal articles, letters/commentaries, and non-peer-reviewed pre-print articles for 1 January-1 July 2020. The primary endpoints were diagnosis of COVID-19 and positive SARS-CoV-2 test. We assessed risk of bias using a tool adapted from the Newcastle-Ottawa Scale. Twelve studies were included in the quantitative synthesis. All four studies of COVID-19 incidence (including 24,181,727 individuals, 125,649 with pre-existing cancer) reported that people with cancer had higher COVID-19 incidence rates. Eight studies reported SARS-CoV-2 test positivity for > 472,000 individuals, 48,370 with pre-existing cancer. Seven of these studies comparing people with any and without cancer, were pooled using random effects [pooled odds ratio 0.91, 95 %CI: 0.57-1.47; unadjusted for age, sex, or comorbidities]. Two studies suggested people with active or haematological cancer had lower risk of a positive test. All 12 studies had high risk of bias; none included universal or random COVID-19/SARS-CoV-2 testing. CONCLUSIONS: The early literature on susceptibility to SARS-CoV-2/COVID-19 for people with cancer is characterised by pervasive biases and limited data. To provide high-quality evidence to inform decision-making, studies of risk of SARS-CoV-2/COVID-19 for people with cancer should control for other potential modifiers of infection risk, including age, sex, comorbidities, exposure to the virus, protective measures taken, and vaccination, in addition to stratifying analyses by cancer type, stage at diagnosis, and treatment received.
-
ItemModeling strategies to analyse longitudinal biomarker data: An illustration on predicting immunotherapy non-response in non-small cell lung cancer(ELSEVIER SCI LTD, 2022-10)Serum tumor markers acquired through a blood draw are known to reflect tumor activity. Their non-invasive nature allows for more frequent testing compared to traditional imaging methods used for response evaluations. Our study aims to compare nine prediction methods to accurately, and with a low false positive rate, predict progressive disease despite treatment (i.e. non-response) using longitudinal tumor biomarker data. Bi-weekly measurements of CYFRA, CA-125, CEA, NSE, and SCC were available from a cohort of 412 advanced stage non-small cell lung cancer (NSCLC) patients treated up to two years with immune checkpoint inhibitors. Serum tumor marker measurements from the first six weeks after treatment initiation were used to predict treatment response at 6 months. Nine models with varying complexity were evaluated in this study, showing how longitudinal biomarker data can be used to predict non-response to immunotherapy in NSCLC patients.
-
ItemThe societal impact of implementing an at-home blood sampling device for chronic care patients: patient preferences and cost impact(BMC, 2022-12-15)BACKGROUND: Diabetes mellitus, cardiovascular diseases, chronic kidney disease, and thyroid diseases are chronic diseases that require regular monitoring through blood tests. This paper first investigates the experiences of chronic care patients with venipuncture and their expectations of an at-home blood-sampling device, and then assesses the impact on societal costs of implementing such a device in current practice. METHODS: An online survey was distributed among chronic care patients to gain insight into their experience of blood sampling in current practice, and their expectations of an at-home blood-sampling device. The survey results were used as input parameters in a patient-level monte carlo analysis developed to represent a hypothetical cohort of Dutch chronically ill patients to investigate the impact on societal costs compared to usual care. RESULTS: In total, 1311 patients participated in the survey, of which 31% experience the time spent on the phlebotomy appointment as a burden. Of all respondents, 71% prefer to use an at-home blood-sampling device to monitor their chronic disease. The cost analysis indicated that implementing an at-home blood-sampling device increases the cost of phlebotomy itself by €27.25 per patient per year, but it reduces the overall societal costs by €24.86 per patient per year, mainly due to limiting productivity loss. CONCLUSIONS: Patients consider an at-home blood-sampling device to be more user-friendly than venous phlebotomy on location. Long waiting times and crowded locations can be avoided by using an at-home blood-sampling device. Implementing such a device is likely cost-saving as it is expected to reduce societal costs.
-
ItemImplementation of Whole-Genome and Transcriptome Sequencing Into Clinical Cancer Care(LIPPINCOTT WILLIAMS & WILKINS, 2022)PURPOSE: The combination of whole-genome and transcriptome sequencing (WGTS) is expected to transform diagnosis and treatment for patients with cancer. WGTS is a comprehensive precision diagnostic test that is starting to replace the standard of care for oncology molecular testing in health care systems around the world; however, the implementation and widescale adoption of this best-in-class testing is lacking. METHODS: Here, we address the barriers in integrating WGTS for cancer diagnostics and treatment selection and answer questions regarding utility in different cancer types, cost-effectiveness and affordability, and other practical considerations for WGTS implementation. RESULTS: We review the current studies implementing WGTS in health care systems and provide a synopsis of the clinical evidence and insights into practical considerations for WGTS implementation. We reflect on regulatory, costs, reimbursement, and incidental findings aspects of this test. CONCLUSION: WGTS is an appropriate comprehensive clinical test for many tumor types and can replace multiple, cascade testing approaches currently performed. Decreasing sequencing cost, increasing number of clinically relevant aberrations and discovery of more complex biomarkers of treatment response, should pave the way for health care systems and laboratories in implementing WGTS into clinical practice, to transform diagnosis and treatment for patients with cancer.
-
ItemA scoping review and meta-analysis on the prevalence of pan-tumour biomarkers (dMMR, MSI, high TMB) in different solid tumours(NATURE PORTFOLIO, 2022-11-28)Immune checkpoint inhibitors have been approved in the USA for tumours exhibiting mismatch repair deficiency (dMMR), microsatellite instability (MSI), or high tumour mutational burden (TMB), with regulatory and reimbursement applications in multiple other countries underway. As the estimated budget impacts of future reimbursements depend on the size of the potential target population, we performed a scoping review and meta-analysis of the prevalence of these pan-tumour biomarkers in different cancers. We systematically searched Medline/Embase and included studies reporting the prevalence of dMMR/MSI/high TMB in solid tumours published 01/01/2018-31/01/2021. Meta-analyses were performed separately for the pan-cancer prevalence of each biomarker, and by cancer type and stage where possible. The searches identified 3890 papers, with 433 prevalence estimates for 32 different cancer types from 201 studies included in meta-analyses. The pooled overall prevalence of dMMR, MSI and high TMB (≥ 10 mutations/Mb) in pan-cancer studies was 2.9%, 2.7% and 14.0%, respectively. The prevalence profiles of dMMR/MSI and high TMB differed across cancer types. For example, endometrial, colorectal, small bowel and gastric cancers showed high prevalence of both dMMR and MSI (range: 8.7-26.8% and 8.5-21.9%, respectively) and high TMB (range: 8.5-43.0%), while cervical, esophageal, bladder/urothelial, lung and skin cancers showed low prevalence of dMMR and MSI (< 5%), but high prevalence of high TMB (range: 23.7-52.6%). For other cancer types, prevalence of all three biomarkers was generally low (< 5%). This structured review of dMMR/MSI/high TMB prevalence across cancers and for specific cancer types and stages provide timely evidence to inform budget impact forecasts in health technology assessments for drug approvals based on these pan-tumour biomarkers.
-
ItemNo Preview AvailableTime to diagnosis and treatment of lung cancer: A systematic overview of risk factors, interventions and impact on patient outcomes(ELSEVIER IRELAND LTD, 2022-04)Over half of patients with lung cancer are diagnosed at a stage when curative treatment is not possible, suggesting an earlier diagnosis could improve outcomes. This comprehensive overview summarises the evidence on 1) times to diagnosis and treatment, 2) their impact on patient outcomes, 3) risk factors and 4) interventions to reduce time intervals, and 5) key methodological issues in such studies. Eligible articles were relevant systematic or scoping reviews and meta-analyses, searched via PubMed, Embase, Web of Science, and Cochrane Library; published from database inception to 6 August 2020 (PROSPERO identifier: CRD42020203530). A total of 18 systematic and scoping reviews were included. Times to diagnosis and treatment significantly varied and were often longer than recommended in international guidelines. Results regarding the impact of time intervals on survival or tumour stage indicated mixed associations (positive, negative, or no); in each review, however, more studies reported either no or negative association. Risk factors were considerable, categorized at the disease, patient, healthcare provider and system levels. Interventions including fast-access diagnosis programs, patient navigation and multidisciplinary strategies were effective in reducing times to diagnosis and treatment. Methodological issues included large variations in interval definitions and summary measures, lack of addressing an important potential source of bias-the "waiting time paradox"-and few studies of trends over time of these intervals. The current evidence indicates that patients with lung cancer experience diagnosis and treatment delays given guidelines' recommendations, but there are inconsistent findings about the association between times to diagnosis and treatment and patient outcomes. This is partially due to variations in definitions of time intervals, and limitations in analytic approaches that fail to account for a potential waiting time paradox. The identified risk factors and effective interventions demonstrate the potential for improvements in addressing diagnostic and treatment delays, regionally and globally.
-
ItemComparing Survival Outcomes for Advanced Cancer Patients Who Received Complex Genomic Profiling Using a Synthetic Control Arm(SPRINGER, 2022-09)BACKGROUND: Complex genomic profiling (CGP) has transformed cancer treatment decision making, yet there is a lack of robust and quantifiable evidence for how utilisation of CGP improves patient outcomes. OBJECTIVE: This study evaluated cohort level clinical effectiveness of CGP to improve overall survival (OS) in real-world advanced cancer patients using a registry-based matched control population. PATIENTS AND METHODS: Two cohorts of advanced and refractory cancer patients were seen in consecutive series for early phase trial enrolment consideration. The first cohort (CGP group) accessed tumour profiling via a research study; while the second cohort that followed was not profiled. Overall survival between cohorts was compared using Kaplan-Meier curves and Cox proportional hazard models. Potential confounding was analysed and adjusted for using stabilised weights based on propensity scores. RESULTS: Within the CGP group, 25 (17.6%) patients received treatment informed by CGP results and this subgroup had significantly improved survival compared with CGP patients in whom results did not impact their treatment (unadjusted HR = 0.44, (0.22-0.88), p = 0.02). However, when comparing the entire CGP cohort with the No CGP cohort, no significant survival benefit was evident with adjusted median OS for CGP of 13.5 months (9.2-17.0) compared with 11.0 (9.2-17.4) for No CGP (adjusted HR = 0.92, (0.65-1.30), p = 0.63). CONCLUSIONS: This study utilised real-world data to simulate a control arm and quantify the clinical effectiveness of genomic testing. The magnitude of survival benefit for patients who had CGP result-led treatments was insufficient to drive an overall survival gain for the entire tested population. Translation of CGP into clinics requires strategies to ensure higher rates of tested patients obtain clinical benefit to deliver on the value proposition of CGP in an advanced cancer population.
-
ItemDo Health Technology Assessment organisations consider manufacturers' costs in relation to drug price? A study of reimbursement reports(BMC, 2022-08-31)INTRODUCTION: Drug reimbursement decisions are often made based on a price set by the manufacturer. In some cases, this price leads to public and scientific debates about whether its level can be justified in relation to its costs, including those related to research and development (R&D) and manufacturing. Such considerations could enter the decision process in collectively financed health care systems. This paper investigates whether manufacturers' costs in relation to drug prices, or profit margins, are explicitly mentioned and considered by health technology assessment (HTA) organisations. METHOD: An analysis of reimbursement reports for cancer drugs was performed. All relevant Dutch HTA-reports, published between 2017 and 2019, were selected and matched with HTA-reports from three other jurisdictions (England, Canada, Australia). Information was extracted. Additionally, reimbursement reports for three cases of expensive non-oncolytic orphan drugs prominent in pricing debates in the Netherlands were investigated in depth to examine consideration of profit margins. RESULTS: A total of 66 HTA-reports concerning 15 cancer drugs were included. None of these reports contained information on manufacturer's costs or profit margins. Some reports contained general considerations of the HTA organisation which related prices to manufacturers' costs: six contained a statement on the lack of price setting transparency, one mentioned recouping R&D costs as a potential argument to justify a high price. For the case studies, 21 HTA-reports were selected. One contained a cost-based price justification provided by the manufacturer. None of the other reports contained information on manufacturer's costs or profit margins. Six reports contained a discussion about lack of transparency. Reports from two jurisdictions contained invitations to justify high prices by demonstrating high costs. CONCLUSION: Despite the attention given to manufacturers' costs in relation to price in public debates and in the literature, this issue does not seem to get explicit systematic consideration in the reimbursement reports of expensive drugs.