Scott D. Ramsey

Randomized Phase III Trial of Paclitaxel Plus Carboplatin Versus Vinorelbine Plus Cisplatin in the Treatment of Patients With Advanced Non–Small-Cell Lung Cancer: A Southwest Oncology Group Trial

PURPOSE This randomized trial was designed to determine whether paclitaxel plus carboplatin (PC) offered a survival advantage over vinorelbine plus cisplatin (VC) for patients with advanced non--small-cell lung cancer. Secondary objectives were to compare toxicity, tolerability, quality of life (QOL), and resource utilization. PATIENTS AND METHODS Two hundred two patients received VC (vinorelbine 25 mg/m(2)/wk and cisplatin 100 mg/m(2)/d, day 1 every 28 days) and 206 patients received PC (paclitaxel 225 mg/m(2) over 3 hours with carboplatin area under the curve of 6, day 1 every 21 days). Patients completed QOL questionnaires at baseline, 13 weeks, and 25 weeks. Resource utilization forms were completed at five time points through 24 months. RESULTS Patient characteristics were similar between the groups. The objective response rate was 28% in the VC arm and 25% in the PC arm. Median survival was 8 months in both arms, with 1-year survival rates of 36% and 38%, respectively. Grade 3 and 4 leukopenia (P =.002) and neutropenia (P =.008) occurred more frequently on the VC arm. Grade 3 nausea and vomiting were higher on the VC arm (P =.001, P =.007), and grade 3 peripheral neuropathy was higher on the PC arm (P <.001). More patients on the VC arm discontinued therapy because of toxicity (P =.001). No difference in QOL was observed. Overall costs on the PC arm were higher than on the VC arm because of drug costs. CONCLUSION PC is equally efficacious as VC for the treatment of advanced non--small-cell lung cancer. PC is less toxic and better tolerated but more expensive than VC. New treatment strategies should be pursued.

Quality of life in survivors of colorectal carcinoma

Colon carcinoma is a common malignancy that accounts for a substantial share of all cancer‐related morbidity and mortality. However, little is known with regard to general and disease specific quality of life in survivors of colorectal carcinoma, particularly from community‐based samples of cases across stage and survival times from diagnosis.

Breast Cancer in Limited-Resource Countries: An Overview of the Breast Health Global Initiative 2005 Guidelines

Abstract:  Breast cancer is the most common cause of cancer‐related death among women worldwide, with case fatality rates highest in low‐resource countries. Despite significant scientific advances in its management, most of the world faces resource constraints that limit the capacity to improve early detection, diagnosis, and treatment of the disease. The Breast Health Global Initiative (BHGI) strives to develop evidence‐based, economically feasible, and culturally appropriate guidelines that can be used in nations with limited health care resources to improve breast cancer outcomes. Using an evidence‐based consensus panel process, four BHGI expert panels addressed the areas of early detection and access to care, diagnosis and pathology, treatment and resource allocation, and health care systems and public policy as they relate to breast health care in limited‐resource settings. To update and expand on the BHGI Guidelines published in 2003, the 2005 BHGI panels outlined a stepwise, systematic approach to health care improvement using a tiered system of resource allotment into four levels—basic, limited, enhanced, and maximal—based on the contribution of each resource toward improving clinical outcomes. Early breast cancer detection improves outcome in a cost‐effective fashion assuming treatment is available, but requires public education to foster active patient participation in diagnosis and treatment. Clinical breast examination combined with diagnostic breast imaging (ultrasound ± diagnostic mammography) can facilitate cost‐effective tissue sampling techniques for cytologic or histologic diagnosis. Breast‐conserving treatment with partial mastectomy and radiation therapy requires more health care resources and infrastructure than mastectomy, but can be provided in a thoughtfully designed limited‐resource setting. The availability and administration of systemic therapies are critical to improving breast cancer survival. Estrogen receptor testing allows patient selection for hormonal treatments (tamoxifen, oophorectomy). Chemotherapy, which requires some allocation of resources and infrastructure, is needed to treat node‐positive, locally advanced breast cancers, which represent the most common clinical presentation of disease in low‐resource countries. When chemotherapy is not available, patients with locally advanced, hormone receptor‐negative cancers can only receive palliative therapy. Future research is needed to better determine how these guidelines can best be implemented in limited‐resource settings.

Washington State Cancer Patients Found To Be At Greater Risk For Bankruptcy Than People Without A Cancer Diagnosis

Much has been written about the relationship between high medical expenses and the likelihood of filing for bankruptcy, but the relationship between receiving a cancer diagnosis and filing for bankruptcy is less well understood. We estimated the incidence and relative risk of bankruptcy for people age twenty-one or older diagnosed with cancer compared to people the same age without cancer by conducting a retrospective cohort analysis that used a variety of medical, personal, legal, and bankruptcy sources covering the Western District of Washington State in US Bankruptcy Court for the period 1995-2009. We found that cancer patients were 2.65 times more likely to go bankrupt than people without cancer. Younger cancer patients had 2-5 times higher rates of bankruptcy than cancer patients age sixty-five or older, which indicates that Medicare and Social Security may mitigate bankruptcy risk for the older group. The findings suggest that employers and governments may have a policy role to play in creating programs and incentives that could help people cover expenses in the first year following a cancer diagnosis.

Antimicrobial Prophylaxis and Outpatient Management of Fever and Neutropenia in Adults Treated for Malignancy: American Society of Clinical Oncology Clinical Practice Guideline

PURPOSE To provide guidelines on antimicrobial prophylaxis for adult neutropenic oncology outpatients and on selection and treatment as outpatients of those with fever and neutropenia. METHODS A literature search identified relevant studies published in English. Primary outcomes included: development of fever and/or infections in afebrile neutropenic outpatients and recovery without complications and overall mortality in febrile neutropenic outpatients. Secondary outcomes included: in afebrile neutropenic outpatients, infection-related mortality; in outpatients with fever and neutropenia, defervescence without regimen change, time to defervescence, infectious complications, and recurrent fever; and in both groups, hospital admissions, duration, and adverse effects of antimicrobials. An Expert Panel developed guidelines based on extracted data and informal consensus. RESULTS Forty-seven articles from 43 studies met selection criteria. RECOMMENDATIONS Antibacterial and antifungal prophylaxis are only recommended for patients expected to have < 100 neutrophils/μL for > 7 days, unless other factors increase risks for complications or mortality to similar levels. Inpatient treatment is standard to manage febrile neutropenic episodes, although carefully selected patients may be managed as outpatients after systematic assessment beginning with a validated risk index (eg, Multinational Association for Supportive Care in Cancer [MASCC] score or Talcotts rules). Patients with MASCC scores ≥ 21 or in Talcott group 4, and without other risk factors, can be managed safely as outpatients. Febrile neutropenic patients should receive initial doses of empirical antibacterial therapy within an hour of triage and should either be monitored for at least 4 hours to determine suitability for outpatient management or be admitted to the hospital. An oral fluoroquinolone plus amoxicillin/clavulanate (or plus clindamycin if penicillin allergic) is recommended as empiric therapy, unless fluoroquinolone prophylaxis was used before fever developed.

Quality of life in long term survivors of colorectal cancer

Abstract OBJECTIVES: We aimed to determine the quality of life (QOL) for long term survivors of colorectal cancer. METHODS: Persons with colorectal cancer who had survived at least 5 yr from diagnosis were recruited from a local cancer registry to answer questions about general QOL and colon cancer-specific issues. Before the general survey, focus group interviews with long term survivors were conducted to select survey questions from a pool of general and cancer-specific QOL questionnaires. The survey included the Health Utilities Index, the Center for Epidemiological Studies Depression Scale, and questions from the Short Form 36 and Functional Assessment of Cancer Therapy-Colorectal Cancer. After permission was obtained from their primary physicians, long term survivors from the registry were mailed invitation letters, then telephoned. Those agreeing were mailed self-administered questionnaires with stamped return envelopes. RESULTS: Two hundred twenty-seven respondents (average age = 74 yr, 46% female) completed the survey. Survivors reported a relatively uniform and high QOL, irrespective of stage at diagnosis and time from diagnosis. Non-cancer related comorbid conditions and low income status had more influence on overall QOL than initial stage of colorectal cancer or time since diagnosis. Compared to age-matched populations, long term survivors reported higher overall QOL, but had higher rates of depression. Sixteen percent reported three or more bowel movements a day; 49% reported chronic recurrent diarrhea. CONCLUSIONS: Those who achieve long term remission from colorectal cancer may experience a relatively high QOL, although physical symptoms such as diarrhea and depressive symptoms remain a problem.

Breast Cancer in Limited-Resource Countries: Health Care Systems and Public Policy

Abstract:   As the largest cancer killer of women around the globe, breast cancer adversely impacts countries at all levels of economic development. Despite major advances in the early detection, diagnosis, and treatment of breast cancer, health care ministries face multitiered challenges to create and support health care programs that can improve breast cancer outcomes. In addition to the financial and organizational problems inherent in any health care system, breast health programs are hindered by a lack of recognition of cancer as a public health priority, trained health care personnel shortages and migration, public and health care provider educational deficits, and social barriers that impede patient entry into early detection and cancer treatment programs. No perfect health care system exists, even in the wealthiest countries. Based on inevitable economic and practical constraints, all health care systems are compelled to make trade‐offs among four factors: access to care, scope of service, quality of care, and cost containment. Given these trade‐offs, guidelines can define stratified approaches by which economically realistic incremental improvements can be sequentially implemented within the context of resource constraints to improve breast health care. Disease‐specific “vertical” programs warrant “horizontal” integration with existing health care systems in limited‐resource countries. The Breast Health Global Initiative (BHGI) Health Care Systems and Public Policy Panel defined a stratified framework outlining recommended breast health care interventions for each of four incremental levels of resources (basic, limited, enhanced, and maximal). Reallocation of existing resources and integration of a breast health care program with existing programs and infrastructure can potentially improve outcomes in a cost‐sensitive manner. This adaptable framework can be used as a tool by policymakers for program planning and research design to make best use of available resources to improve breast health care in a given limited‐resource setting.

Risk of Rehospitalization for Patients Using Clopidogrel With a Proton Pump Inhibitor

BACKGROUND Recent pharmacodynamic and retrospective clinical analyses have suggested that proton pump inhibitors (PPIs) may modify the antiplatelet effects of clopidogrel bisulfate. METHODS We conducted a retrospective cohort study of persons enrolled in a multistate health insurance plan with commercial and Medicare clients to evaluate adverse clinical outcomes in patients using clopidogrel plus a PPI compared with clopidogrel alone. Patients who were discharged from the hospital after myocardial infarction (MI) or coronary stent placement and treated with clopidogrel plus a PPI (n = 1033) were matched 1:1 (using propensity scoring) with patients with similar cardiovascular risk factors treated with clopidogrel alone. Rehospitalizations for MI or coronary stent placement were evaluated for up to 360 days. A subanalysis was conducted to study the impact of pantoprazole sodium, the most used PPI. RESULTS Patients who received clopidogrel plus a PPI had a 93% higher risk of rehospitalization for MI (adjusted hazard ratio, 1.93; 95% confidence interval, 1.05-3.54; P = .03) and a 64% higher risk of rehospitalization for MI or coronary stent placement (1.64; 1.16-2.32; P = .005) than did patients receiving clopidogrel alone. Increased risk of rehospitalization for MI or coronary stent placement was also observed for the subgroup of patients receiving clopidogrel plus pantoprazole (adjusted hazard ratio, 1.91; 95% confidence interval, 1.19-3.06; P = .008). CONCLUSIONS Patients who received clopidogrel plus a PPI had a significantly higher risk of rehospitalization for MI or coronary stent placement than did patients receiving clopidogrel alone. Prospective clinical trials and laboratory analyses of biochemical interactions are warranted to further evaluate the potential impact of PPIs on the efficacy of clopidogrel.

Using Generalized Linear Models to Assess Medical Care Costs

Medical expenditure data typically exhibit certain characteristics that must be accounted for when deriving cost estimates. First, it is common for a small percentage of patients to incur extremely high costs compared to other patients, resulting in a distribution of expenses that is highly skewed to the right. Second, the assumption of homoscedasticity (constant variance) is often violated because expense data exhibit variability that increases as the mean expense increases. In this paper, we describe the use of the generalized linear model for estimating costs, and discuss several advantages that this technique has over traditional methods of cost analysis. We provide an example, applying this technique to the problem of determining an incidence-based estimate of the cost of care for patients with diabetes who suffer a stroke.

Cost-Effectiveness Analysis Alongside Clinical Trials II—An ISPOR Good Research Practices Task Force Report

Clinical trials evaluating medicines, medical devices, and procedures now commonly assess the economic value of these interventions. The growing number of prospective clinical/economic trials reflects both widespread interest in economic information for new technologies and the regulatory and reimbursement requirements of many countries that now consider evidence of economic value along with clinical efficacy. As decision makers increasingly demand evidence of economic value for health care interventions, conducting high-quality economic analyses alongside clinical studies is desirable because they broaden the scope of information available on a particular intervention, and can efficiently provide timely information with high internal and, when designed and analyzed properly, reasonable external validity. In 2005, ISPOR published the Good Research Practices for Cost-Effectiveness Analysis Alongside Clinical Trials: The ISPOR RCT-CEA Task Force report. ISPOR initiated an update of the report in 2014 to include the methodological developments over the last 9 years. This report provides updated recommendations reflecting advances in several areas related to trial design, selecting data elements, database design and management, analysis, and reporting of results. Task force members note that trials should be designed to evaluate effectiveness (rather than efficacy) when possible, should include clinical outcome measures, and should obtain health resource use and health state utilities directly from study subjects. Collection of economic data should be fully integrated into the study. An incremental analysis should be conducted with an intention-to-treat approach, complemented by relevant subgroup analyses. Uncertainty should be characterized. Articles should adhere to established standards for reporting results of cost-effectiveness analyses. Economic studies alongside trials are complementary to other evaluations (e.g., modeling studies) as information for decision makers who consider evidence of economic value along with clinical efficacy when making resource allocation decisions.