Objective
Various statistical methods have been developed to estimate hazard ratios (HRs) from published Kaplan‐Meier (KM) curves for the purpose of performing meta‐analyses. The objective of this ...study was to determine the reliability, accuracy, and precision of four commonly used methods by Guyot, Williamson, Parmar, and Hoyle and Henley.
Design
Pivotal randomized controlled trials (RCTs) in oncology were identified from the pan‐Canadian Oncology Drug Review (pCODR) database (primary analysis) and the Food and Drug Administration's (FDA) drug approvals page (secondary analysis) between January 2012 and May 2016. Two reviewers independently reconstructed HRs using each method on KM curves extracted from each trial and compared them with reported HRs (gold standard). Bland‐Altman plots and summary statistics were calculated to assess accuracy and precision of these methods. Interrater reliability was assessed using intraclass correlation coefficient (ICC). These four methods were also applied to KM curves of different structures (ie, flat versus steep curves).
Results
A total of 118 KM curves (55 RCTs) and 77 KM curves (46 RCTs) were extracted from pCODR and FDA, respectively. In the primary analysis, the Guyot method was the most accurate with the lowest mean error (0.0094; 95% CI, −0.0012‐0.020). All four methods had excellent interrater reliability. The Guyot method showed the smallest bias and greatest precision on the Bland‐Altman plots. The Guyot method was consistently superior in both the secondary and all sensitivity analyses.
Conclusion
In the absence of reported HRs, we recommend that researchers consider the Guyot method to reconstruct HRs from KM curves when performing aggregate data meta‐analyses.
Purpose
In the past decade, literature has called attention to financial toxicities experienced by cancer patients. Though studies have addressed research questions in high-income countries, there ...remains a paucity of in-depth reviews regarding low- and middle-income countries (LMICs). Our scoping review provides an overview of treatment-related financial toxicities experienced by cancer patients in LMICs.
Methods
A systematic search was conducted in MEDLINE, EMBASE and the Cochrane Central Register of Controlled Trials. English peer-reviewed articles that (a) explored patients’ experience with financial toxicity due to cancer treatment (b) were specific to LMICs as defined by the World Bank and (c) focused on qualitative data were included. Details regarding participants and main findings were extracted and synthesized.
Results
The search yielded 6290 citations, and 42 studies across 3 low-income, 9 lower-middle-income and 8 upper-middle-income countries. Main themes identified included cancer patients encountered various material hardships, managed costs with different coping behaviours and experienced negative psychological responses to their financial burden. Higher levels of financial toxicities were associated with patient characteristics such as lower socio-economic status and lack of insurance, as well as patient outcomes such as lower quality of life.
Conclusion
Cancer patients in LMIC experience deleterious financial toxicities as a result of treatment. This comprehensive characterization of financial toxicities will better allow health systems to adopt evidence-based mitigation strategies to reduce the financial burden on patients.
Background. Experience from treating patients with Spanish influenza and influenza A(H5N1) suggested that convalescent plasma therapy might be beneficial. However, its efficacy in patients with ...severe pandemic influenza A(H1N1) 2009 virus (H1N1 2009) infection remained unknown. Methods. During the period from 1 September 2009 through 30 June 2010, we conducted a prospective cohort study by recruiting patients aged ≥ 18 years with severe H1N1 2009 infection requiring intensive care. Patients were offered treatment with convalescent plasma with a neutralizing antibody titer of ≥1:160, harvested by apheresis from patients recovering from H1N1 2009 infection. Clinical outcome was compared with that of patients who declined plasma treatment as the untreated controls. Results. Ninety-three patients with severe H1N1 2009 infection requiring intensive care were recruited. Twenty patients (21.5%) received plasma treatment. The treatment and control groups were matched by age, sex, and disease severity scores. Mortality in the treatment group was significantly lower than in the nontreatment group (20.0% vs 54.8%; P = .01). Multivariate analysis showed that plasma treatment reduced mortality (odds ratio OR, .20; 95% confidence interval CI, .06-.69; P = .011), whereas complication of acute renal failure was independently associated with death (OR, 3.79; 95% CI, 1.15-12.4; P = .028). Subgroup analysis of 44 patients with serial respiratory tract viral load and cytokine level demonstrated that plasma treatment was associated with significantly lower day 3, 5, and 7 viral load, compared with the control group (P < .05). The corresponding temporal levels of interleukin 6, interleukin 10, and tumor necrosis factor α (P < .05) were also lower in the treatment group. Conclusions. Treatment of severe H1N1 2009 infection with convalescent plasma reduced respiratory tract viral load, serum cytokine response, and mortality.
The rapidly intensifying process of ocean acidification (OA) due to
anthropogenic CO2 is not only depleting carbonate ions necessary
for calcification but also causing acidosis and disrupting ...internal pH
homeostasis in several marine organisms. These negative consequences of OA on
marine calcifiers, i.e. oyster species, have been very well documented in
recent studies; however, the consequences of reduced or impaired
calcification on the end-product, shells or skeletons, still remain one of
the major research gaps. Shells produced by marine organisms under OA are
expected to show signs of dissolution, disorganized microstructure and
reduced mechanical properties. To bridge this knowledge gap and to test the
above hypothesis, we investigated the effect of OA on juvenile shells of the
commercially important oyster species, Magallana angulata,
at ecologically and climatically relevant OA levels (using pH 8.1, 7.8, 7.5,
7.2). In lower pH conditions, a drop of shell hardness and stiffness was
revealed by nanoindentation tests, while an evident porous internal
microstructure was detected by scanning electron microscopy. Crystallographic
orientation, on the other hand, showed no significant difference with
decreasing pH using electron back-scattered diffraction (EBSD). These results
indicate the porous internal microstructure may be the cause of the reduction
in shell hardness and stiffness. The overall decrease of shell density observed
from micro-computed tomography analysis indicates the porous internal
microstructure may run through the shell, thus inevitably limiting the
effectiveness of the shell's defensive function. This study shows the potential
deterioration of oyster shells induced by OA, especially in their early life
stage. This knowledge is critical to estimate the survival and production of
edible oysters in the future ocean.
IMPORTANCE: Melanoma treatment has evolved during the past decade with the adoption of adjuvant and palliative immunotherapy and targeted therapies, with an unclear impact on health care costs and ...outcomes in routine practice. OBJECTIVE: To examine changes in health care costs, overall survival (OS), and time toxicity associated with primary treatment of melanoma. DESIGN, SETTING, AND PARTICIPANTS: This cohort study assessed a longitudinal, propensity score (PS)–matched, retrospective cohort of residents of Ontario, Canada, aged 20 years or older with stages II to IV cutaneous melanoma identified from the Ontario Cancer Registry from January 1, 2018, to March 31, 2019. A historical comparison cohort was identified from a population-based sample of invasive melanoma cases diagnosed from the Ontario Cancer Registry from January 1, 2007, to December 31, 2012. Data analysis was performed from October 17, 2022, to March 13, 2023. EXPOSURES: Era of melanoma diagnosis (2007-2012 vs 2018-2019). MAIN OUTCOMES AND MEASURES: The primary outcomes were mean per-capita health care and systemic therapy costs (Canadian dollars) during the first year after melanoma diagnosis, time toxicity (days with physical health care contact) within 1 year of initial treatment, and OS. Standardized differences were used to compare costs and time toxicity. Kaplan-Meier methods and Cox proportional hazards regression were used to compare OS among PS-matched cohorts. RESULTS: A PS-matched cohort of 731 patients (mean SD age, 67.9 14.8 years; 437 59.8% male) with melanoma from 2018 to 2019 and 731 patients (mean SD age, 67.9 14.4 years; 440 60.2% male) from 2007 to 2012 were evaluated. The 2018 to 2019 patients had greater mean (SD) health care (including systemic therapy) costs compared with the 2007 to 2012 patients ($47 886 $55 176 vs $33 347 $31 576), specifically for stage III ($67 108 $57 226 vs $46 511 $30 622) and stage IV disease ($117 450 $79 272 vs $47 739 $37 652). Mean (SD) systemic therapy costs were greater among 2018 to 2019 patients: stage II ($40 823 $40 621 vs $10 309 $12 176), III ($55 699 $41 181 vs $9764 $12 771), and IV disease ($79 358 $50 442 vs $9318 $14 986). Overall survival was greater for the 2018 to 2019 cohort compared with the 2007 to 2012 cohort (3-year OS: 74.2% 95% CI, 70.8%-77.2% vs 65.8% 95% CI, 62.2%-69.1%, hazard ratio, 0.72 95% CI, 0.61-0.85; P < .001). Time toxicity was similar between eras. Patients with stage IV disease spent more than 1 day per week (>52 days) with physical contact with the health care system by 2018 to 2019 (mean SD, 58.7 43.8 vs 44.2 26.5 days; standardized difference, 0.40; P = .20). CONCLUSIONS AND RELEVANCE: This cohort study found greater health care costs in the treatment of stages II to IV melanoma and substantial time toxicity for patients with stage IV disease, with improvements in OS associated with the adoption of immunotherapy and targeted therapies. These health system–wide data highlight the trade-off with adoption of new therapies, for which there is a greater economic burden to the health care system and time burden to patients but an associated improvement in survival.
While no direct comparative data exist for crizotinib in ROS1+ non-small cell lung cancer (NSCLC), studies have suggested clinical benefit with this targeted agent. The objective of this study was to ...assess the cost-effectiveness of crizotinib compared to standard platinum-doublet chemotherapy for first-line treatment of ROS1+ advanced NSCLC.
A Markov model was developed with a 10-year time horizon from the perspective of the Canadian publicly-funded health care system. Health states included progression-free survival (PFS), up to two further lines of therapy post-progression, palliation and death. Given a lack of comparative data and small study samples, crizotinib or chemotherapy studies with advanced ROS1+ NSCLC patients were identified and time-to-event data from digitized Kaplan-Meier curves were collected to pool PFS data. Costs of drugs, treatment administration, monitoring, adverse events and palliative care were included in 2018 Canadian dollars, with 1.5% discounting. An incremental cost-effectiveness ratio (ICER) was estimated probabilistically using 5000 simulations.
In the base-case probabilistic analysis, crizotinib produced additional 0.885 life-years and 0.772 quality-adjusted life-years (QALYs) at an incremental cost of $238,077, producing an ICER of $273,286/QALY gained. No simulations were found to be cost-effective at a willingness-to-pay threshold of $100,000/QALY gained. A scenario analysis assuming efficacy equivalent to the ALK+ NSCLC population showed a slightly more favorable cost-effectiveness profile for crizotinib.
Available data appear to support superior activity of crizotinib compared to chemotherapy in ROS1+ advanced NSCLC. At the list price, crizotinib was not cost-effective at commonly accepted willingness-to-pay thresholds across a wide range of sensitivity analyses.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Rhinovirus is a common cause of upper and lower respiratory tract infections in adults, especially among the elderly and immunocompromised. Nevertheless, its clinical characteristics and mortality ...risks have not been well described. A retrospective analysis on a prospective cohort was conducted in a single teaching hospital center over a one-year period. We compared adult patients hospitalized for pneumonia caused by rhinovirus infection with those hospitalized for influenza infection during the same period. All recruited patients were followed up for at least 3 months up to 15 months. Independent risk factors associated with mortality for rhinovirus infection were identified. Between 1 March 2014 and 28 February 2015, a total of 1946 patients were consecutively included for analysis. Of these, 728 patients were hospitalized for rhinovirus infection and 1218 patients were hospitalized for influenza infection. Significantly more rhinovirus patients were elderly home residents and had chronic lung diseases (
< 0.001), whereas more influenza patients had previous stroke (
= 0.02); otherwise, there were no differences in the Charlson comorbidity indexes between the two groups. More patients in the rhinovirus group developed pneumonia complications (
= 0.03), required oxygen therapy, and had a longer hospitalization period (
< 0.001), whereas more patients in the influenza virus group presented with fever (
< 0.001) and upper respiratory tract symptoms of cough and sore throat (
< 0.001), and developed cardiovascular complications (
< 0.001). The 30-day (
< 0.05), 90-day (
< 0.01), and 1-year (
< 0.01) mortality rate was significantly higher in the rhinovirus group than the influenza virus group. Intensive care unit admission (odds ratio (OR): 9.56; 95% confidence interval (C.I.) 2.17-42.18), elderly home residents (OR: 2.60; 95% C.I. 1.56-4.33), requirement of oxygen therapy during hospitalization (OR: 2.62; 95% C.I. 1.62-4.24), and hemoglobin level <13.3 g/dL upon admission (OR: 2.43; 95% C.I. 1.16-5.12) were independent risk factors associated with 1-year mortality in patients hospitalized for rhinovirus infection. Rhinovirus infection in the adults was associated with significantly higher mortality and longer hospitalization when compared with influenza virus infection. Institutionalized older adults were particularly at risk. More stringent infection control among health care workers in elderly homes could lower the infection rate before an effective vaccine and antiviral become available.
Extrapolation of time-to-event data from clinical trials is commonly used in decision models for health technology assessment (HTA). The objective of this study was to assess performance of standard ...parametric survival analysis techniques for extrapolation of time-to-event data for a single event from clinical trials with limited data due to small samples or short follow-up.
Simulated populations with 50,000 individuals were generated with an exponential hazard rate for the event of interest. A scenario consisted of 5000 repetitions with six sample size groups (30-500 patients) artificially censored after every 10% of events observed. Goodness-of-fit statistics (AIC, BIC) were used to determine the best-fitting among standard parametric distributions (exponential, Weibull, log-normal, log-logistic, generalized gamma, Gompertz). Median survival, one-year survival probability, time horizon (1% survival time, or 99th percentile of survival distribution) and restricted mean survival time (RMST) were compared to population values to assess coverage and error (e.g., mean absolute percentage error).
The true exponential distribution was correctly identified using goodness-of-fit according to BIC more frequently compared to AIC (average 92% vs 68%). Under-coverage and large errors were observed for all outcomes when distributions were specified by AIC and for time horizon and RMST with BIC. Error in point estimates were found to be strongly associated with sample size and completeness of follow-up. Small samples produced larger average error, even with complete follow-up, than large samples with short follow-up. Correctly specifying the event distribution reduced magnitude of error in larger samples but not in smaller samples.
Limited clinical data from small samples, or short follow-up of large samples, produce large error in estimates relevant to HTA regardless of whether the correct distribution is specified. The associated uncertainty in estimated parameters may not capture the true population values. Decision models that base lifetime time horizon on the model's extrapolated output are not likely to reliably estimate mean survival or its uncertainty. For data with an exponential event distribution, BIC more reliably identified the true distribution than AIC. These findings have important implications for health decision modelling and HTA of novel therapies seeking approval with limited evidence.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
PDF
