Beth Sherrill

Attempts to quit smoking and relapse: Factors associated with success or failure from the ATTEMPT cohort study

OBJECTIVE To identify predictors of attempts to stop smoking and predictors of relapse. METHODS This study included 2431 smokers from pre-existing Internet panels in the United States, United Kingdom, Canada, France, and Spain. These panel members are Internet users who have registered voluntarily and agreed to participate in various online research studies. Respondents were aged 35-65 years, smoked >or= five cigarettes per day and intended to stop smoking in the next 3 months. They were followed every 3 months for up to 18 months via Internet contact on measures relating to quit attempts, smoking status, motivation to quit, nicotine cue, weight and weight concern, health-related factors, withdrawal symptoms, and smoking cessation aids. RESULTS In this study, recent quit attempts strongly predicted future attempts, but also predicted subsequent relapse. Motivation to quit was predictive of future attempts but not of relapse/abstinence following the attempts. Relapse to smoking was associated with nicotine dependence, exposure to smoking cues, craving, withdrawal symptoms, and lack of smoking cessation aids. CONCLUSIONS The findings lend support to a model of cessation in which level of motivation to stop generates quit attempts but plays little role in relapse. Dependence, social smoking cues, and a recently failed quit attempt are important factors in relapse.

The US postmarketing surveillance study of adult osteosarcoma and teriparatide: Study design and findings from the first 7 years

The Osteosarcoma Surveillance Study, an ongoing 15‐year surveillance study initiated in 2003, is a postmarketing commitment to the United States (US) Food and Drug Administration to evaluate a potential association between teriparatide, rhPTH(1–34), a recombinant human parathyroid hormone analog (self‐injectable medication to treat osteoporosis), and development of osteosarcoma in response to a finding from preclinical (animal) studies. Incident cases of primary osteosarcoma diagnosed in adults (aged ≥40 years) on or after January 1, 2003, are identified through population‐based state, regional, and comprehensive cancer center registries in the US. Information on possible prior treatment with teriparatide, on demographics, and on risk factors is ascertained by patient or proxy telephone interview after patient consent. Between June 2004 and September 30, 2011, 1448 cases (diagnosed 2003 to 2009) were identified by participating cancer registries (estimated to be 62% of all adult cases in the US for that time period); 549 patients or proxies were interviewed. Interviewed patients were similar to noninterviewed patients with regard to mean age, sex, race, and geographical distribution and tumor type and site of tumor. Mean age of those interviewed was 61 years, 46% were female, 86% were white, and 77% were alive when the case was reported to the study investigators. Data collected in the study provide descriptive information on a large number of adults with osteosarcoma, an uncommon malignant bone tumor. After 7 years of the study, there were no osteosarcoma patients who had a prior history of teriparatide treatment. Thus, approximately halfway through this 15‐year study, the study has not detected a pattern indicative of a causal association between teriparatide treatment and osteosarcoma in humans.

Single‐Pill vs Free‐Equivalent Combination Therapies for Hypertension: A Meta‐Analysis of Health Care Costs and Adherence

J Clin Hypertens (Greenwich). 2011;13:898–909. ©2011 Wiley Periodicals, Inc.

Effect of Persistent Moderate Viremia on Disease Progression During HIV Therapy

ObjectiveAlthough highly active antiretroviral therapy has been shown to lower plasma HIV-1 RNA in HIV infection, many patients do not reach the target goal of undetectable viremia. We evaluated whether risk of clinical progression varies by level of viral suppression achieved. DesignPatients in the Collaborations in HIV Outcomes Research/United States cohort who maintained stable HIV-1 RNA levels of either <400, 400 to 20,000, or >20,000 copies/mL during a run-in period of at least 6 months were studied. Baseline was the first day after this period. MethodsProportional hazards models were used to quantify the relation between baseline HIV-1 RNA levels and risk of a new AIDS-defining diagnosis or death after adjusting for CD4 count, age, gender, ethnicity, study site, prior AIDS-defining diagnosis, and antiretroviral therapy history. ResultsPatients (N = 3010) were followed for up to 4.3 years after the 6-month run-in period, with 343 deaths or AIDS-defining diagnoses reported. The risk of a new AIDS-defining diagnosis or death was not significantly different in the 400 to 20,000– and <400-copies/mL groups (6% vs. 7%, hazard ratio [HR] = 1.0, 95% confidence interval [CI]: 0.7–1.4; P = 0.9) but was significantly higher in the >20,000-copies/mL group (26%, HR = 3.3, 95% CI: 2.5–4.4; P < 0.001 vs. the <400-copies/mL group). Median CD4 count changes during the first year of follow-up showed increases of 75 and 13 cells/mm3 for the <400- and 400 to 20,000–copies/mL groups, respectively, whereas the >20,000-copies/mL group had a decrease of 23 cells/mm3. ConclusionsPatients who maintained baseline HIV-1 RNA levels of 400 to 20,000 copies/mL for at least 6 months preserved immunologic status and were no more likely to die or develop a new AIDS-defining diagnosis in the time frame studied than those with baseline levels <400 copies/mL. Patients with HIV-1 RNA levels >20,000 copies/mL at baseline had greater clinical and immunologic deterioration. These data suggest that maintenance of moderate viremia may confer clinical benefit not seen when viremia exceeds 20,000 copies/mL, and this should be taken into account when considering the risks and benefits of continuing failing therapy.

Review of meta-analyses evaluating surrogate endpoints for overall survival in oncology.

Overall survival (OS) is the gold standard in measuring the treatment effect of new drug therapies for cancer. However, practical factors may preclude the collection of unconfounded OS data, and surrogate endpoints are often used instead. Meta-analyses have been widely used for the validation of surrogate endpoints, specifically in oncology. This research reviewed published meta-analyses on the types of surrogate measures used in oncology studies and examined the extent of correlation between surrogate endpoints and OS for different cancer types. A search was conducted in October 2010 to compile available published evidence in the English language for the validation of disease progression-related endpoints as surrogates of OS, based on meta-analyses. We summarize published meta-analyses that quantified the correlation between progression-based endpoints and OS for multiple advanced solid-tumor types. We also discuss issues that affect the interpretation of these findings. Progression-free survival is the most commonly used surrogate measure in studies of advanced solid tumors, and correlation with OS is reported for a limited number of cancer types. Given the increased use of crossover in trials and the availability of second-/third-line treatment options available to patients after progression, it will become increasingly more difficult to establish correlation between effects on progression-free survival and OS in additional tumor types.

Three-year posttransplant graft survival in renal-transplant patients with graft function at 6 months receiving tacrolimus or cyclosporine microemulsion within a triple-drug regimen

Background. Registry data can provide valuable information about possible treatment effects; however, pretreatment differences in patient characteristics may influence treatment assignment. Careful analysis must therefore be undertaken when evaluating treatment differences in the context of nonrandomized studies so that the impact of treatment selection bias is minimized. Methods. A multivariable risk factor analysis of adult patients registered in the US Renal Data System who received a primary renal allograft during 1995 to 1998 was undertaken to compare 3-year graft survival using tacrolimus or Neoral with mycophenolate mofetil (MMF) and steroids. Results. In total, 9,449 patients were included (cadaveric donor n=6,011; living donor n=3,438). Patients (2,130) received tacrolimus, and 7,319 received Neoral. At 3 years posttransplant, the proportion of cadaveric donor recipients experiencing all causes of graft loss was 10.0% for tacrolimus and 10.6% for Neoral; for living donor recipients these figures were 6.5% and 6.7%, respectively (unadjusted Kaplan-Meier analysis). The incidence of graft failure excluding death was also similar between the two groups. With Cox proportional hazards modeling, the adjusted relative hazard of 3-year graft failure for cadaveric donor patients taking tacrolimus versus Neoral was 1.02 (95% confidence interval [CI] 0.8–1.3), and for living-donor recipients it was 1.15 (95% CI 0.8–1.8). Conclusions. These results indicate excellent 3-year graft survival for both cadaveric and living-donor renal-transplant patients receiving either Neoral or tacrolimus with MMF and steroids, with no significant differences between treatment groups. On the basis of these results, relative cost-effectiveness may become increasingly important in selection of tacrolimus or Neoral as primary immunosuppressant for renal-transplant patients.

Quality of Life in Hormone Receptor–Positive HER-2+ Metastatic Breast Cancer Patients During Treatment with Letrozole Alone or in Combination with Lapatinib

This paper presents analyses evaluating quality of life in patients with hormone receptor–positive human epidermal growth factor receptor 2–positive tumors receiving letrozole alone or in combination with lapatinib in clinical trial EGF30008.

PROCEED: Prospective Obesity Cohort of Economic Evaluation and Determinants: baseline health and healthcare utilization of the US sample

Aim:  To summarize baseline characteristics, health conditions, resource utilization and resource cost for the US population for the 90‐day period preceding enrolment, stratified by body mass index (BMI) and the presence of abdominal obesity (AO).

Meta-analysis of the association between progression-free survival and overall survival in metastatic colorectal cancer

PurposeThe validity of progression-free survival (PFS) as a surrogate endpoint for overall survival (OS) in metastatic colorectal cancer (mCRC) trials has been studied, primarily in first-line treatment. The relationship between PFS and OS has not been well studied in later lines of treatment.MethodsWe conducted a systematic literature review of mCRC phase 2 and 3 clinical trials that reported OS and PFS (or time-to-progression [TTP]) data. Correlation between endpoints (either PFS alone or PFS aggregated with TTP [PFS_TTP]) was estimated within treatment arms. Treatment effect was the ratio of the median time to OS, PFS, or PFS_TTP in the “control” versus “experimental” arm. We conducted meta-regression analyses and performed receiver-operating characteristic (ROC) analysis.ResultsWe analyzed data from 62 articles (23,527 patients). A high positive correlation was found between median PFS_TTP and median OS within treatment arms (r = 0.87; 95% confidence interval [CI], 0.82–0.91) and also between the median OS and median PFS (r = 0.89, 95% CI, 0.83–0.93)]. R2 was 0.48 for PFS_TTP and 0.59 for PFS; R2 for PFS_TTP was higher for first-line (R2 = 0.54) than second-line studies (R2 = 0.38). The ROC analysis is presented as a conceptual tool for evaluating the performance of PFS as a surrogate for OS at various thresholds.ConclusionsThe correlation of PFS, alone or aggregated with TTP, with OS in clinical trials of patients with mCRC is robust across lines of therapy and provides a useful means of predicting improvements in OS using PFS data.

Impact of Waist Circumference Difference on Health‐Care Cost among Overweight and Obese Subjects: The PROCEED Cohort

OBJECTIVE To estimate the incremental effect of waist circumference (WC) on health-care costs among overweight and obese subjects after adjusting for body mass index (BMI). METHODS A prospective study. The subjects were members of Internet panels in the United States (US) and Germany. 10,816 individuals (United States: n = 5410; Germany: n = 5406) aged 30-70 years with BMI scores between 20 and 35 kg/m(2) were recruited and grouped by category: healthy weight (BMI 20-24.9 kg/m(2)), overweight (BMI 25-29.9 kg/m(2)), and obese (BMI 30-35 kg/m(2)). Within the overweight and obese categories, the individuals were stratified by sex and within those subgroups, characterized as above or below the median WC. The subjects self-reported weight, WC, and health-care resource use at baseline, 3 months, and 6 months using online questionnaires. Over 65% of the recruited subjects completed all surveys. Resource utilization was translated into health-care costs by multiplying unit costs from national sources in each country. Annualized health costs were summarized for subjects with low and high WC within the overweight and obese categories. A two-part model generated predicted annual costs because of the WC difference controlling for BMI, demographic, and lifestyle variables among the overweight and obese subjects. RESULTS When BMI and other characteristics are constant, annual health-care costs are 16% to 18% higher in Germany and 20% to 30% higher in the United States for the subjects with a high WC compared with subjects with a low WC. CONCLUSIONS Targeting people with a high waist circumference for weight management whether they are overweight or obese may maximize cost-efficacy.