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Biomedical subjects

C C Earle

Publications and source records attributed to C C Earle.

At least 19 recordsLinked to original sources
PubMed2006

Computed tomography screening for lung cancer in Hodgkin's lymphoma survivors: decision analysis and cost-effectiveness analysis.

BACKGROUND: Hodgkin's lymphoma patients have an elevated risk of developing lung cancer and may be targeted for lung cancer screening. We used a decision-analytic model to estimate the potential clinical benefits and cost-effectiveness of computed tomography (CT) screening for lung cancer in Hodgkin's lymphoma survivors. MATERIALS AND METHODS: We developed a Markov decision-analytic model to compare annual low-dose CT screening versus no screening in a hypothetical cohort of patients diagnosed with stage IA-IIB Hodgkin's lymphoma at age 25, with screening starting 5 years after initial diagnosis. We derived model parameters from published studies and the Surveillance, Epidemiology and End Results (SEER) Program, and assumed that stage-shift produces a survival benefit. RESULTS: Annual CT screening increased survival by 0.64 years for smokers and 0.16 years for non-smokers. The corresponding benefits in quality-adjusted survival were 0.58 quality-adjusted life-years (QALYs) for smokers and 0.14 QALYs for non-smokers. The incremental cost-effectiveness ratios for annual CT screening compared with no screening were $34 100/QALY for smokers and $125 400/QALY for non-smokers. CONCLUSIONS: Our analysis suggests that if early promising results for lung cancer screening hold, CT screening for lung cancer may increase survival and quality-adjusted survival among Hodgkin's lymphoma survivors, with a benefit and incremental cost-effectiveness ratio for smokers comparable to that of other recommended cancer screening strategies.

Aged↗
PubMed2003

Cancer physicians' attitudes toward colorectal cancer follow-up.

BACKGROUND: The optimal follow-up strategy for colorectal cancer is unknown. MATERIALS AND METHODS: We surveyed all Canadian radiation oncologists, medical oncologists and surgeons specializing in colorectal cancer to assess their recommendations for follow-up after potentially curative treatment, the beliefs and attitudes underlying these practices, and the cost implications of different follow-up strategies. RESULTS: One hundred and sixty practitioners (58%) returned completed surveys. Most recommended clinical assessments every 3-4 months in the first 2 years including carcino-embryonic antigen testing, gradually decreasing in frequency over 5 years. Ninety per cent recommend a surveillance colonoscopy in the first year. The majority felt that specialist involvement in follow-up was important because of the increased opportunities for patients to contribute to research (76%) and teaching (73%). About half felt that specialists were more efficient at providing follow-up than primary care physicians, but these same physicians recommended significantly longer and more expensive follow-up routines on average than others. Primary care physicians were felt to be important allies, especially in managing the psychosocial concerns of patients. CONCLUSIONS: Surveillance practices are generally in keeping with published recommendations. Most specialists feel that they should remain involved in follow-up, but this may result in increased resource utilization.

Adult↗
PubMed2001

Effectiveness of chemotherapy for advanced lung cancer in the elderly: instrumental variable and propensity analysis.

PURPOSE: To compare the effectiveness of chemotherapy given to elderly patients in routine practice for stage IV non-small-cell lung cancer (NSCLC) with the efficacy observed in randomized trials. PATIENTS AND METHODS: We used instrumental variable analysis (IVA) and propensity scores (PS) to simulate the conditions of a randomized trial in a retrospective cohort of patients over age 65 from the Survival, Epidemiology, and End Results (SEER) tumor registry. Geographic variation in chemotherapy use served as the instrument for the IVA analysis, and propensity scores were calculated with a logistic model based on patient disease and sociodemographic characteristics. RESULTS: Among 6,232 elderly patients, the instrumental variable estimate indicated an increase in median survival of 33 days and an improvement in 1-year survival of 9% attributable to chemotherapy. In a Cox regression model, chemotherapy administration was associated with a hazard ratio of 0.81 (95% confidence interval, 0.76 to 0.85). When survival was analyzed separately within propensity score quintiles, the hazard ratios were all similar, ranging from 0.78 to 0.85. These results are comparable with those of a large meta-analysis, which found a hazard ratio of 0.87 in the subgroup of patients over age 65. CONCLUSION: Chemotherapy for stage IV NSCLC seems to have effectiveness for elderly patients and those with comorbid conditions that is similar to the efficacy seen in randomized trials containing mostly younger, highly selected patients. All suitable patients should be given the opportunity to consider palliative chemotherapy for metastatic NSCLC.

Aged↗
PubMed2001

Potential cost-effectiveness of one-time screening for lung cancer (LC) in a high risk cohort.

The development of low-dose helical computed-tomography (CT) scanning to detect nodules as small as a few mm has sparked renewed interest in lung cancer (LC) screening. The objective of this study was to assess the potential health effects and cost-effectiveness of a one-time low-dose helical CT scan to screen for LC. We created a decision analysis model using baseline results from the Early Lung Cancer Action Project (ELCAP); Surveillance, Epidemiology and End Results (SEER) registry public-use database; screening program costs estimated from 1999 Medicare reimbursement rates; and annual costs of managing cancer and non-cancer patients from Riley et al. (1995) [Med Care 1995;33(8):828-841] and Taplin et al. (1995) [J Natl Cancer Inst 1995;87(6):417-26]. The main outcome measures included years of life, cost estimates of baseline diagnostic screening and follow up, and cost-effectiveness of screening. We found that in a very high-risk cohort (LC prevalence of 2.7%) of patients between 60 and 74 years of age, a one-time screen appears to be cost-effective at $5940 per life year saved. In a lower risk general population of smokers (LC prevalence of 0.7%), a one-time screen appears to be cost-effective at $23100 per life year. Even when a lead-time bias of 1 year is incorporated into the model for a low risk population, the cost-effectiveness is estimated at $58183 per life year. Based on the assumptions embedded in this model, one-time screening of elderly high-risk patients for LC appears to be cost-effective.

Aged↗
PubMed2001

Economic decision analysis model of screening for lung cancer.

The objective of this study was to evaluate the potential clinical and economic implications of an annual lung cancer screening programme based on helical computed tomography (CT). A decision analysis model was created using combined data from the Surveillance, Epidemiology and End Results (SEER) registry public-use database and published results from the Early Lung Cancer Action Project (ELCAP). We found that under optimal conditions in a high risk cohort of patients between 60 and 74 years of age, annual lung cancer screening over a period of 5 years appears to be cost effective at approximately $19000 per life year saved. A sensitivity analysis of the model to account for a 1-year decrease in survival benefit and changes in assumptions for incidence rate and costs generated cost effectiveness estimates ranging from approximately $10800 to $62000 per life year saved. Based on the assumptions embedded in this model, annual screening of high risk elderly patients for lung cancer may be cost effective under optimal conditions, but longer term data are needed to confirm if this will be borne out in practice.

Aged↗
PubMed2001

Thymidylate synthase expression in stage II and III colon cancer: a retrospective review.

This study is a retrospective analysis of thymidylate synthase (TS) levels in patients with stage II (T3 or T4) and III colon cancer. Two groups of patients were identified: one undergoing surgery alone (98 patients) and the second receiving adjuvant 5-fluorouracil chemotherapy (112 patients). TS analyses were carried out using the 106 monoclonal antibody and a published grading system dividing staining into high and low intensity. The distribution of patients with low versus high TS levels was similar in the two groups. There was no association between TS staining intensity and grade, stage or location of primary. Seventy-nine patients have relapsed: 46 (48%) in the surgery only group, 33 (30%) in the adjuvant therapy group (median follow-up: 51 and 61 months). Similar proportions relapsed when analyzed according to TS: in the surgery only group, 41% of patients with low TS, 48% with high TS; in the adjuvant group, 31% with low TS, 30% with high TS. In the surgery only group, a trend toward improved disease-free survival (DFS) was seen in the low TS group (84 versus 63% at 2 years, p = 0.08). No difference was seen in overall survival. There were no differences in DFS or overall survival in patients receiving adjuvant therapy according to TS intensity. The trend for worse outcome in patients with high TS is consistent with previous reports. The lack of difference in outcome for patients with low and high TS receiving chemotherapy suggests that high TS levels may predict greater benefit from adjuvant treatment.

Aged↗
PubMed2000

Systematic overview of cost-utility assessments in oncology.

PURPOSE: Cost-utility analyses (CUAs) present the value of an intervention as the ratio of its incremental cost divided by its incremental survival benefit, with survival weighted by utilities to produce quality-adjusted life years (QALYs). We critically reviewed the CUA literature and its role in informing clinical oncology practice, research priorities, and policy. METHODS: The English-language literature was searched between 1975 and1997 for CUAs. Two readers abstracted from each article descriptions of the clinical situation and patients, the methods used, study perspective, the measures of effectiveness, costs included, discounting, and whether sensitivity analyses were performed. The readers then made subjective quality assessments. We also extracted utility values from the reviewed papers, along with information on how and from whom utilities were measured. RESULTS: Our search yielded 40 studies, which described 263 health states and presented 89 cost-utility ratios. Both the number and quality of studies increased over time. However, many studies are at variance with current standards. Only 20% of studies took a societal perspective, more than a third failed to discount both the costs and QALYs, and utilities were often simply estimates from the investigators or other physicians. CONCLUSION: The cost-utility literature in oncology is not large but is rapidly expanding. There remains much room for improvement in the methodological rigor with which utilities are measured. Considering quality-of-life effects by incorporating utilities into economic studies is particularly important in oncology, where many therapies obtain modest improvements in response or survival at the expense of nontrivial toxicity.

Clinical Trials as Topic↗
PubMed2000

Decision framework for chemotherapeutic interventions for metastatic non-small-cell lung cancer.

BACKGROUND: Best supportive care has long been considered to be the standard therapy for metastatic non-small-cell lung cancer (NSCLC). There is now evidence from randomized trials that a number of chemotherapy regimens can palliate cancer-related symptoms and modestly improve survival. We show how cost-effectiveness analyses can be used to make choices between different (ambulatory) chemotherapy regimens. METHODS: Clinical algorithms describing the diagnosis, staging, and treatment of metastatic NSCLC were incorporated into Statistics Canada's Population Health Model. Using consistent methodology, we assessed the cost-effectiveness of several chemotherapeutic interventions: a combination of vindesine (VDS) plus cisplatin, etoposide (VP-16) plus cisplatin, vinblastine (VLB) plus cisplatin, vinorelbine (Navelbine; NVB) plus cisplatin, paclitaxel (Taxol) plus cisplatin, and gemcitabine (GEM) and NVB alone. We calculated the total chemotherapy costs in 1995 Canadian dollars, the cost per case, the average life-years saved, and the cost per life-year saved. Using the Population Health Model, we then constructed an advanced decision framework that rank-ordered the various treatment regimens so as to optimize benefit below various cost-effectiveness thresholds. RESULTS: One regimen (VLB plus cisplatin) appears to result in better survival and lower health care expenditures than best supportive care. By use of cost-effectiveness thresholds of $25,000 and $50,000 per life-year gained, NVB plus cisplatin is the preferred regimen. When quality of life is considered, however, GEM is preferred to NVB plus cisplatin at a threshold value of $50,000. At thresholds of $75 000 and $100,000, paclitaxel plus cisplatin at a dose of 135 mg/m(2) is the preferred regimen. At thresholds of $50,000 and above, best supportive care is the least preferred regimen. CONCLUSIONS: This decision framework allows the comparison of different treatment regimens based on various cost-effectiveness thresholds. Our analysis also supports the use of chemotherapy regimens and the abandonment of best supportive care as the standard of care for patients with advanced NSCLC. [J Natl Cancer Inst 2000;92:1321-9].

Algorithms↗
PubMed2000

Outcomes research in oncology: history, conceptual framework, and trends in the literature.

"Outcomes research" is a commonly used term, but what does it really mean? In this review article, we 1) briefly review the historic background of outcomes research, paying particular attention to the social and political movements that helped shape the field; 2) present a conceptual framework to help classify the major areas of research and provide a working definition of outcomes research; and 3) review the oncology literature in the English language from 1966 through 1998 to examine temporal trends and characterize the body of work being presented to the practicing oncology community. We conclude that outcomes research is a broad concept, which, in its current usage, describes an array of distinct types of research. However, common themes are apparent when outcomes research is viewed in the context of its historic origins and is contrasted with other established disciplines, especially clinical trials. Our literature review shows that outcomes studies are increasing in absolute numbers, in relative proportion of the oncology literature, and in quality. We suggest that as different branches of investigation develop their own literature and methodology-in effect, outgrowing the generic label of outcomes research-they become identified by separate, more precise terms.

Cost-Benefit Analysis↗
PubMed2000

Who gets chemotherapy for metastatic lung cancer?

STUDY OBJECTIVES: To determine the prevalence and factors associated with chemotherapy use in elderly patients presenting with advanced lung cancer. DESIGN: A retrospective cohort study using administrative data. SETTING AND PATIENTS: We analyzed the medical bills for the 6,308 Medicare patients > 65 years old with diagnosed stage IV non-small cell lung cancer (NSCLC) in the 11 SEER (survival, epidemiology, and end results) regions between 1991 and 1993. The main outcome measure, chemotherapy administration, was identified by the relevant medical billing codes. Patient sociodemographic and disease characteristics were obtained from the SEER database and census data. RESULTS: Almost 22% of patients received chemotherapy at some time for their metastatic NSCLC. As expected, younger patients and those with fewer comorbid conditions were more likely to receive chemotherapy. However, several nonmedical factors, such as nonblack race, higher socioeconomic status, treatment in a teaching hospital, and living in the Seattle/Puget Sound or Los Angeles SEER regions, also significantly increased a patient's likelihood of receiving chemotherapy. CONCLUSION: Compared to previous reports, the prevalence of chemotherapy use for advanced NSCLC appears to be increasing. However, despite uniform health insurance coverage, there is wide variation in the utilization of palliative chemotherapy among Medicare patients, and nonmedical factors are strong predictors of whether a patient receives chemotherapy. While it is impossible to know the appropriate rate of usage, nonmedical factors should only influence a patient's likelihood of receiving treatment if they reflect patient treatment preference. Research to further clarify the costs, benefits, and patient preferences for chemotherapy in this patient population is warranted in order to minimize the effect of nonmedical biases on management decisions.

Aged↗
PubMed1999

Adjuvant chemotherapy after curative resection for gastric cancer in non-Asian patients: revisiting a meta-analysis of randomised trials.

UNLABELLED: The aim of this study was to assess whether adjuvant chemotherapy after curative resection of gastric cancer increases survival rates. DATA SOURCES: MEDLINE (1966-1999), CancerLit (1983-1999), bibliographies, personal reprint files, and review articles were searched for relevant articles. Studies had to be randomised controlled trials of adjuvant chemotherapy versus observation following curative resection of stomach cancer that took place in non-Asian countries. Two reviewers independently evaluated the trials for eligibility, quality assessment and data abstraction, 13 trials met the eligibility criteria. The odds ratio for death in the treated group was 0.80 (95% confidence interval (CI) 0.66-0.97), corresponding to a relative risk of 0.94 (95% CI 0.89-1.00). Subgroup analyses showed a trend towards a larger magnitude of the effect when analysis was restricted to trials in which at least 2/3 of patients had node-positive disease. Our results suggest that adjuvant chemotherapy may produce a small survival benefit of borderline statistical significance in patients with curatively resected gastric carcinoma. Continued trials to find and confirm an effective adjuvant strategy are warranted.

Chemotherapy, Adjuvant↗
PubMed1999

Cost-effectivenes of paclitaxel plus cisplatin in advanced non-small-cell lung cancer.

The aim of this study was to assess the cost-effectiveness of combination chemotherapy with paclitaxel/cisplatin, compared with standard etoposide/cisplatin in patients with advanced non-small cell lung cancer (NSCLC). We obtained the primary survival and resource utilization data from a large three-arm randomized trial comparing: paclitaxel 135 mg m(-2) by 24-h intravenous (i.v.) infusion + cisplatin; paclitaxel 250 mg m(-2) by 24-h i.v. infusion + cisplatin + granulocyte colony-stimulating factor (G-CSF); and standard etoposide/cisplatin in patients with stage IIIb or IV NSCLC. We also modelled the regimens with paclitaxel 135 mg m(-2) + cisplatin administered as an outpatient by 3-h infusion, as clinical data suggest that this is equivalent to 24-h infusion. We collected costing data from the Ottawa Regional Cancer Centre and applied it to the resources consumed in the randomized trial. We integrated these data into the Statistics Canada POpulation HEalth Model (POHEM), which generated hypothetical cohorts of patients treated with each regimen. The POHEM model assigned diagnostic work-up, treatment, disease progression and survival characteristics to each individual in these cohorts and tabulated the costs associated with each. We did sensitivity analyses around the costs of chemotherapy and its administration, and the survival differences between the two regimens. All costs are in 1997 Canadian dollars ($1.00 Canadian approximately Pound 0.39 sterling). The perspective is that of the Canadian health care system. In the trial, the two paclitaxel-containing arms had almost identical survival curves with a median survival of 9.7 months compared with 7.4 months for etoposide/cisplatin. As administered in the trial, paclitaxel/cisplatin cost $76,370 per life-year gained (LYG) and paclitaxel/cisplatin/G-CSF $138,578 per LYG relative to etoposide/cisplatin. However, when modelled as an outpatient 3-h infusion, paclitaxel/cisplatin was moderately cost-effective at $30,619 per LYG. When compared with historical controls treated with best supportive care, this regimen of paclitaxel/cisplatin cost $4539 per LYG. Assuming a 3-h paclitaxel infusion yields the same survival advantage as the 24-h infusion did in the randomized trial, paclitaxel/cisplatin is a cost-effective improvement over standard etoposide/cisplatin for patients with advanced non-small cell lung cancer.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1998

A phase I study of gemcitabine/cisplatin/etoposide in the treatment of small-cell lung cancer.

PURPOSE: To define the maximum tolerated dose and toxicity of combined cisplatin, etoposide, and gemcitabine in patients with small-cell lung cancer. METHODS: We undertook a phase I study in patients with either extensive small-cell lung cancer with or without prior chemotherapy, or limited disease who had progressed or recurred despite prior treatment. Patients received cisplatin 75 mg/m2 i.v. day 1, etoposide 50-100 mg/m2 i.v. day 1 followed by oral administration of 50-100 mg/m2 days 2 5, and gemcitabine at either 800 or 1000 mg/m2 i.v. days 1 and 8, on a 3 weekly cycle. RESULTS: We treated 20 patients, 14 at the 800 mg/m2 gemcitabine dose level, and six at the 1000 mg/m2 dose level. The protocol initially used an etoposide dose of 100 mg/m2 etoposide daily (i.v. day 1 and orally days 2-5), but the first two patients died of septic complications. With reduction of the etoposide dose to 50 mg/m2 daily x 5, the regimen was well tolerated. At this etoposide dose, neutropenia, mucositis, and gastrointestinal toxicity occurred in one patient at each of the two gemcitabine dose levels. In addition, one patient receiving gemcitabine at the 1000 mg/m2 level experienced a possible allergic reaction. The overall response rate was 54%. Patients on gemcitabine at the 800 mg/m2 level who had not received prior chemotherapy had the highest response rate, at 75%. CONCLUSION: The recommended phase II doses for this regimen are cisplatin 75 mg/m2 i.v. day 1, etoposide 50 mg/m2 i.v. day 1 and orally days 2-5, and gemcitabine 800 mg/m2 i.v. days 1 and 8. Future trials should further examine the optimal relative doses and schedule of gemcitabine and etoposide.

Adult↗
PubMed1998

Cost-effectiveness analysis in oncology.

Physicians are faced with a burgeoning literature of economic studies. However, most physicians have little training in evaluating economic research. Economic studies involve a comparison of the costs and benefits of alternative treatment options. To be of use for medical decision making, they should meet appropriate methodological standards. These include clear specification of the research question and the perspective from which the study is being undertaken, comparison of relevant treatment options, identification and quantification of all important costs and benefits, the use of discounting to allow for time preferences for costs and benefits, and sensitivity analyses to test the robustness of the study's results. Unfortunately, not all adhere to these principles. Physicians need to be able to understand and critically assess the quality of economic studies, and the applicability of the results to their own situation, in order to participate in medical policy decisions.

Cost-Benefit Analysis↗
PubMed1997

Phase II study of a one hour paclitaxel infusion in combination with carboplatin for advanced non-small cell lung cancer.

PURPOSE: To determine the activity, toxicity, and optimal dose of paclitaxel when given by one hour infusion combined with carboplatin in advanced non-small cell lung cancer (NSCLC). PATIENTS AND METHODS: Thirty-seven previously untreated patients with stage IIIB or IV NSCLC were enrolled. Paclitaxel was administered by one hour infusion at a dose of 175 mg/m2 for the first cycle, and was escalated up to 255 mg/m2 over successive cycles if tolerated. In the absence of toxicity, the carboplatin dose was kept constant at an area under the concentration-time curve (AUC) of 6. Cycles were repeated at 3-week intervals until progression or intolerable toxicity occurred. RESULTS: Thirty-six patients were evaluable for toxicity and survival, and thirty-five for responses. The partial response rate was 10 of 35 (29%) and there were no complete responses. The median duration of response was 4.8 months (range 0.5-11.7 months). The median survival duration was 6.5 months, and 1 year survival was 31%. The mean paclitaxel dose was 188 mg/m2. Treatment was generally well tolerated. Four patients (11%) had febrile neutropenia. Five patients (14%) had grade 3 neuropathy, and 4 (11%) had grade 3 nausea and vomiting. Minor toxicities included alopecia, myalgias, arthralgias and stomatitis. CONCLUSIONS: Paclitaxel and carboplatin is a well-tolerated regimen that can safely be given by a one hour paclitaxel infusion. The modest response rate observed in this study may be due to either the low dose-intensity of paclitaxel or the short infusion duration. Further trials to optimize the relative doses of paclitaxel and carboplatin are needed.

Adult↗
PubMed1997

Cost of combined modality interventions for stage III non-small-cell lung cancer.

PURPOSE: To evaluate the cost-effectiveness (CE) of new combined modality strategies in patients with stage III non-small-cell lung cancer (NSCLC). METHODS: Recent studies suggest that combined modality therapy confers a survival advantage for patients with stage III NSCLC. Using the Statistics Canada (Ottawa, Canada) lung cancer costing model, we have evaluated the CE of these interventions using 1993 Canadian health care costs and the perspective of the government as payer in a universal health care system. RESULTS: We estimate that the cost to treat a stage IIIa NSCLC patient with preoperative and postoperative chemotherapy would increase by $15,886, and a similar combined modality approach with the addition of postoperative radiotherapy would increase the cost by $22,963. Chemoradiotherapy for stage IIIb NSCLC would produce a smaller incremental cost of approximately $8,912 per case. However, these approaches are remarkably cost-effective, with cost per life-year gained (LYG) ranging from $3,348 to $14,958. Administering all chemotherapy in the outpatient department would improve CE. For sensitivity analysis, we reduced the survival gain that resulted from the three interventions by 25% and 50%, and increased the hospital per diem rates by 10%, 20%, and 30%. CONCLUSION: Even with the most adverse assumptions, the CE estimates were all considered acceptable for new health care technologies in Canada. Overall, it appears that neoadjuvant therapy for stage IIIa NSCLC and combined modality therapy for stage IIIb NSCLC are cost-effective. Economic considerations should not be a barrier to their adoption.

Antineoplastic Combined Chemotherapy Protocols↗