Models in the development of clinical practice guidelines.

Clinical practice guidelines should be based on the best scientific evidence derived from systematic reviews of primary research. However, these studies often do not provide evidence needed by guideline development groups to evaluate the tradeoffs between benefits and harms. In this article, the authors identify 4 areas where models can bridge the gaps between published evidence and the information needed for guideline development applying new or updated information on disease risk, diagnostic test properties, and treatment efficacy; exploring a more complete array of alternative intervention strategies; assessing benefits and harms over a lifetime horizon; and projecting outcomes for the conditions for which the guideline is intended. The use of modeling as an approach to bridge these gaps (provided that the models are high-quality and adequately validated) is considered. Colorectal and breast cancer screening are used as examples to show the utility of models for these purposes. The authors propose that a modeling study is most useful when strong primary evidence is available to inform the model but critical gaps remain between the evidence and the questions that the guideline group must address. In these cases, model results have a place alongside the findings of systematic reviews to inform health care practice and policy.

Comparative effectiveness research in practice and policy for radiation oncology.

Interest in comparative effectiveness research (CER) has increased dramatically over the past decade, yet perceptions about what comprises CER varies. CER has several attributes relevant to practice and policy: (1) The goal of CER is to inform decisions about health care. (2) Literature synthesis is used in addition to primary research. (3) CER evaluates not only overall outcomes for the population but also evaluates subgroups that may have heterogeneous outcomes. (4) Research places an emphasis on outcomes in the "real-world" settings. (5) Outcomes studied should be relevant to patients. In radiation oncology, where many of the traditional clinical trials are comparative in nature, the line between CER and "traditional" research may be blurred, but an increased emphasis on CER can help to bridge the research enterprise and clinical practice, helping to inform decision making at the patient, clinician, and policy levels.

Economic evaluation alongside a clinical trial of psycho-educational interventions to improve adjustment to survivorship among patients with breast cancer.

PURPOSE: There is little economic research on psychosocial interventions. We aimed to collect data alongside a randomized trial to compare the costs and benefits of three psycho-educational strategies to improve transition to cancer survivorship. METHODS: We evaluated the incremental delivery costs per unit increase in energy (using the Medical Outcomes Study vitality scale) or decrease in distress (from the Revised Impact of Events Scale) in the 6 months postintervention. We also evaluated 1-year post-treatment health care costs. RESULTS: The costs of the control, video, and video plus counseling arms were $11.30, $25.85, and $134.47 per person, respectively. The video costs were $2.22 per unit increase in energy compared with control; among women who were the least prepared for transition, the video was more effective, resulting in even lower costs. The video cost $7,275 per unit change in distress versus control, but costs were lower in the subgroup least prepared for transition ($355). The counseling arm was more expensive and less effective than the video for virtually all end points. However, in one group, women more prepared for transition, counseling cost $1,066 per unit decrease in distress compared with the video. Health care costs tended to increase as intervention intensity increased. CONCLUSION: There are no standards for evaluating cost-effectiveness of trials with psychosocial end points. In this trial, the educational video was the most cost-effective way to improve transition to survivorship. It will be important to confirm whether there is an increased use of services after such interventions and if this represents appropriate use of rehabilitative and supportive care or over-use.

Health limitations and quality of life associated with cancer and other chronic diseases by phase of care.

OBJECTIVE: To estimate health limitations and health-related quality of life (HRQL) associated with cancer and other chronic conditions in a nationally representative sample within a phase-of-care framework. STUDY DESIGN AND SETTING: We used a nested case-control design to assess health limitations and HRQL in individuals reporting a breast, colorectal, prostate, or lung cancer diagnosis, or a diagnosis of arthritis, diabetes, heart disease, or hypertension compared with similar controls without these conditions. All subjects were selected from the 1986-1994 National Health Interview Surveys linked to mortality files in 1995, and classified into the initial, continuing, or last year of life phase of care. Health limitations and HRQL were compared for cases and controls for each condition with 2-sided statistical tests. RESULTS: Across all conditions, individuals in the last year of life phase of care reported greater health limitations and lower HRQL, as measured by the Health Activities and Limitations Index (HALex), than did individuals in the initial and continuing phases of care. Compared with their matched controls, individuals with cancer or other chronic conditions were more likely to report health limitations and lower mean HALex values in the initial, continuing, and last year of life phases of care (P < 0.05). CONCLUSIONS: We observed greater health limitations and lower HRQL associated with cancer and other chronic diseases compared with similar individuals without these conditions. The phase-of-care framework used in this study seems to be applicable to the assessment of HRQL for cancer and other chronic diseases.

Process utility in breast biopsy.

PURPOSE: To determine whether the waiting trade-off (WTO) is feasible for differentiating short-term biopsy preferences in an acute situation where anxiety is the symptomatic disease state. METHODS: 75 women with past experience of either breast core-needle biopsy (CNB), more invasive excisional surgical biopsy (EXB), or both, had telephone WTO assessments. Patients' baseline and test-related anxiety were valued by time trade-off (TTO) used to scale the WTO. Rating scales (RS) were obtained for convergent validity assessment with WTO and TTO. RESULTS: Data were obtained in 38 women who had both CNB and EXB ("paired") and 20 who had CNB only and 16 who had EXB only ("unpaired"). Patients rated only the procedure(s) they experienced. Median paired and mean unpaired WTO scores indicated patients were willing to wait significantly longer to avoid EXB (P = 0.0003, P = 0.0002, respectively). The waiting time difference between EXB and CNB was 2.1 weeks greater in unpaired data than paired data. RS scores comparing the procedures were significantly different only for paired data (P < 0.05). Median TTO preferences for baseline (1.00) and test anxiety (0.93) obtained in 74 patients were significantly different (P < 0.0001) and consistent with RS. Correlation was noted between WTO and RS (-0.307 to -0.453, P = 0.0205 to 0.0001). The median EXB quality-adjusted life years toll (1.5 quality-adjusted life days) calculated from pooled WTO data (paired and unpaired) from 54 patients is near a threshold in a published model. CONCLUSION: The WTO is feasible for discriminating preferences for short-term health states in an acute medical scenario where it might have been expected to be impracticable.

Cost-effectiveness analysis based on the atypical squamous cells of undetermined significance/low-grade squamous intraepithelial lesion Triage Study (ALTS).

BACKGROUND: The ALTS (atypical squamous cells of undetermined significance [ASCUS] and low-grade squamous intraepithelial lesion [LSIL] Triage Study) suggests that, for women diagnosed with ASCUS, human papillomavirus (HPV) DNA testing followed by referral to colposcopy of only those women with oncogenic HPV (i.e., HPV DNA testing) is as effective at detecting cervical intraepithelial neoplasia (CIN) 3 or cancer (CIN3+) as referring all women with ASCUS for immediate colposcopy. We conducted a cost-effectiveness analysis of the ALTS trial to determine whether HPV DNA testing is a cost-effective alternative to immediate colposcopy or conservative management with up to three cytology examinations. METHODS: Data from the ALTS trial were used in conjunction with medical care costs in a short-term decision model. The model compared the incremental costs per case of CIN3+ detected as measured by the incremental cost-effectiveness ratio (ICER) for the following management strategies for women with ASCUS: immediate colposcopy, HPV DNA testing, and conservative management with up to three cytology examinations. RESULTS: The least costly and least sensitive strategy was conservative management with one repeat cytology examination using a threshold of high-grade squamous intraepithelial lesion (HSIL) for referral to colposcopy. Compared with this strategy, triage to colposcopy based on a positive HPV DNA test result had an ICER of 3517 dollars per case of CIN3+ detected. Immediate colposcopy and conservative management with up to three repeat cytology visits detected fewer cases of CIN3+ and were more costly than HPV DNA testing. Immediate colposcopy became cost-effective at 20,370 dollars compared with HPV DNA testing only if colposcopy and biopsy were assumed to be 100% sensitive. CONCLUSIONS: HPV DNA testing is an economically viable strategy for triage of ASCUS cytology. The less than perfect sensitivity of colposcopy and biopsy needs to be accounted for in future clinical guidelines and policy analyses.

Patterns of care in early-stage breast cancer survivors in the first year after cessation of active treatment.

PURPOSE: Patterns of health care use have not been well described for breast cancer survivors. The purpose of this study was to describe the health service use in a survivor cohort. PATIENTS AND METHODS: Women with stage I or II breast cancer were recruited (n = 558) after primary treatment for a multicenter, randomized trial of psychoeducational interventions for facilitating transition to survivorship; 418 women completed the study. Participants completed calendar diaries detailing health care use for 1 year after treatment. Services were coded using Current Procedural Terminology-Fourth Edition codes; costs were estimated using year 2000 Medicare reimbursements. RESULTS: Health care use diary data were available for 391 women (70% of the sample). On average, these survivors reported 30 episodes of health service use in the year after treatment. Total annual costs of care averaged more than 1,800 dollars per survivor; medical office visits were the major component of costs. Type of cancer treatment, depression, and physical function and comorbid illness were independent predictors of the costs of services. There were geographic variations in initial local treatment patterns and in post-treatment costs. Notably, all women should have received surveillance mammography in the time period, but only 61.9% did so; the odds of mammogram receipt were higher for women who had a lumpectomy (v mastectomy) and women who were white (v nonwhite). CONCLUSION: Use of health services is frequent and intensive in the first year after treatment for breast cancer. Despite frequent contact with the health care system, there is room for improvement in providing guideline-suggested surveillance mammography for survivors.

Federal sponsorship of cost-effectiveness and related research in health care: 1997-2001.

OBJECTIVES: To describe recent federal sponsorship of cost-effectiveness and related health economics research to provide insight into the functioning of existing research support systems and assess the roles of federal health agencies. METHODS: Using the PubMed database, we identified cost-effectiveness and related publications citing support from a US government entity and published during the period of 1997 through 2001, and audited them for information on funding sources, study type, and content focus. RESULTS: Five Department of Health and Human Services agencies and centers and the Veterans Administration are cited as funders in 74% of 520 federally supported health economics publications we identified. Three-fourths of federally supported publications address five areas of high disease burden: infections, cancer, HIV/AIDS, cardiovascular disease, and substance abuse. Other high burden diseases, including mental health, diabetes, and injuries, receive less attention. Federal support of health economics studies of health education and care delivery-intervention types underexamined in the field-is relatively strong but most often focuses on substance abuse or mental health services. Each of the top federal funders has a distinct funding pattern, but there are substantial areas of overlap within which we could not identify content domains specific to one funder or another. CONCLUSIONS: Federal support of health economics research has paralleled growth in the field. Federal funders support projects consistent with their mission and focus on high-burden disease areas. However, overlapping funding areas, ambiguity concerning agency interests within overlapping content areas, and gaps in some disease and intervention areas suggest that the coordination of health economics research funding could be improved.

Geographic disparities in cervical cancer mortality: what are the roles of risk factor prevalence, screening, and use of recommended treatment?

CONTEXT: Despite advances in early detection and prevention of cervical cancer, women living in rural areas, and particularly in Appalachia, the rural South, the Texas/Mexico border, and the central valley of California, have had consistently higher rates of cervical cancer mortality than their counterparts in other areas during the past several decades. METHODS: This paper reviews the published literature from 1966 to July 2002 to assess three potential pathways underlying this excess mortality--high human papilloma virus (HPV) prevalence, lack of or infrequent screening and advanced disease at diagnosis, and under-use of recommended treatment and shorter survival. FINDINGS: Living in rural areas may impose barriers to cervical cancer control, including lack of transportation and medical care infrastructures. Population characteristics that place women at greater risk for developing and dying from cervical cancer, such as low income, lack of health insurance, and physician availability, are concentrated in rural areas. Published data, however, are insufficient to identify the key reasons for the observed mortality patterns. CONCLUSIONS: At this time, given the lack of definitive evidence in the published literature, decisions about priorities in areas with high rates of cervical cancer mortality will depend on knowledge of current levels of screening, incidence, and stage distribution; and service delivery infrastructures, resources, and acceptability of interventions to the target population.

Burden of illness in cancer survivors: findings from a population-based national sample.

BACKGROUND: Population trends in aging and improved cancer survival are likely to result in increased cancer prevalence in the United States, but few estimates of the burden of illness among cancer survivors are currently available. The purpose of this study was to estimate the burden of illness in cancer survivors in a national, population-based sample. METHODS: A total of 1823 cancer survivors and 5469 age-, sex-, and educational attainment-matched control subjects were identified from the 2000 National Health Interview Survey. Multiple measures of burden, including utility, a summary measure of health, and days lost from work, were compared using two-sided tests of statistical significance for the two groups overall and for subgroups stratified by tumor site and time since diagnosis. RESULTS: Compared with matched control subjects, cancer survivors had poorer outcomes across all burden measures (P<.01). Cancer survivors had lower utility values (0.74 versus 0.80; P<.001) and higher levels of lost productivity and were more likely to report their health as fair or poor (31.0% versus 17.9%; P<.001) than matched control subjects. Cancer survivors reported statistically significantly higher burden than did control subjects across tumor sites and across time since diagnosis (i.e., within the past year, 2-5 years, 6-10 years, and > or =11 years for the majority of measures. CONCLUSIONS: Cancer survivors have poorer health outcomes than do similar individuals without cancer across multiple burden measures. These decrements are consistent across tumor sites and are found in patients many years following reported diagnosis. Improved measurement of long-term burden of illness will be important for future prospective research.

Short-term impact of cancer prevention and screening activities on quality of life.

PURPOSE: There are few data on the short-term effects of participating in cancer prevention activities, undergoing genetic risk assessment, or having routine screening. The objective of this article is to systematically review existing research on short-term effects of prevention, genetic counseling and testing, and screening activities on quality of life. METHODS: We conducted a MEDLINE search for original research studies that were published between January 1, 1985, and December 31, 2002, and conducted in North America or Western Europe. Data were abstracted and summarized using a standardized format. RESULTS: We reviewed 210 publications. Most studies focused on psychological states (anxiety, depression), symptoms, or general health status. One hundred thirty-one studies used 51 previously validated noncancer instruments. Many researchers (12.6%) also added cancer-specific measures, such as perceived cancer risk or symptom indices. Only one study measured satisfaction or quality of provider-client communication. While one report examined lost workdays, no other economic consequences of short-term outcomes were evaluated. Among seven studies that assessed short-term outcomes preferences, only four specifically used time trade-off or linear rating scale methods. No study used standard gamble or willingness-to-pay methods. The overwhelming majority of research indicated that short-term effects were transient. Only two studies linked short-term effects to long-term cancer-related health behaviors such as repeat screening. CONCLUSION: There is considerable heterogeneity in short-term outcome measurement. Clinicians need to be aware of potential for short-term, transient adverse effects. The impact of short-term experiences should to be linked to long-term health status and use of services.

Acceptability of diagnostic tests for breast cancer.

PURPOSE: To assess the acceptability of new non-invasive breast cancer diagnostic tests intended to triage women in need of biopsy. METHODS: Women who had abnormal screening tests and had been recommended to have a biopsy were invited to receive digital mammography, magnetic resonance imaging (MRI), and nuclear medicine evaluation (Tc-99m-sestamibi scanning) before biopsy. Participants completed a questionnaire about satisfaction and acceptability of the procedures. Satisfaction measured women's overall and test-specific satisfaction. Acceptability was measured by self-reported discomfort, embarrassment and women's preference in terms of willingness to pay to avoid a biopsy. RESULTS: Women were satisfied with all of the potential diagnostic triage procedures. Most found the tests more comfortable than a routine mammogram (47, 50, and 66% undergoing MRI, digital mammography, and sestamibi scanning, respectively). Women who provided a response to willingness to pay questions (N = 43) were willing to pay an average of 611 dollars to have a test instead of a biopsy, if the test was as accurate as biopsy. The willingness to pay significantly decreased to 308 dollars if the test only had 95% accuracy. Those who had prior benign breast disease were less willing to pay for a test with 95% accuracy than those without this history. CONCLUSION: Instead of immediate biopsy after an abnormal screening, these results suggest that women would find non-invasive triage tests acceptable, or preferable to biopsy if they were equally accurate or nearly equally accurate as a biopsy. New technologies to diagnose breast cancer should focus on decreasing discomfort as well as increasing test accuracy.

Development of an Interactive Decision Aid for Female BRCA1/BRCA2 Carriers.

Shared decision making between patients and providers is becoming increasingly common, particularly when there is no clear preferred course of action. As a result, decision aids are being adopted with growing frequency and have been applied to many medical decision-making issues. One such issue where there is uncertainty is breast cancer risk management among BRCA1/BRCA2 carriers. We present the development of a CD-ROM decision aid to facilitate risk management decision making in this population. Our decision aid was developed with the intention of providing it through a randomized clinical trial. The CD-ROM is a multimedia, interactive intervention which provides information about breast cancer, risks associated with BRCA1 and BRCA2 mutations, risk management options for hereditary breast cancer, and a breast cancer risk management decision aid. The goal of this CD-ROM, offered as an adjunctive intervention, is to reduce decisional conflict and psychological distress and improve comprehension of risk information, decisional satisfaction, medical adherence, and quality of life for this population of women at increased risk for breast cancer.

Costs and benefits of different strategies to screen for cervical cancer in less-developed countries.

BACKGROUND: About 80% of cervical cancers occur in less-developed countries. This disproportionate burden of cervical cancer in such countries is due mainly to the lack of well-organized screening programs. Several cervical cancer screening strategies have been proposed as more cost-effective than cytology screening. We compared the costs and benefits of different strategies and their effectiveness in saving lives in a less-developed country. METHODS: We used a population-based simulation model to evaluate the incremental societal costs and benefits in Thailand of seven screening techniques, including visual inspection of the cervix after applying acetic acid (VIA), human papillomavirus (HPV) testing, Pap smear, and combinations of screening tests, and examined the discounted costs per year of life saved (LYS). RESULTS: Compared with no (i.e., not well-organized) screening, all strategies saved lives, at costs ranging from 121 US dollars to 6720 US dollars per LYS, and reduced mortality, by up to 58%. Comparing each strategy with the next least expensive alternative, VIA performed at 5-year intervals in women of ages 35-55 with immediate treatment if abnormalities are found was the least expensive option and saved the greatest number of lives, with a cost of 517 US dollars per LYS. HPV screening resulted in similar costs and benefits, if the test cost is 5 US dollars and if 90% of women undergo follow-up after an abnormal screen. Cytology (Pap smear) was a reasonable alternative if sensitivity exceeds 80% and if 90% of women undergo follow-up. Compared with no screening, use of a combination of Pap smear and HPV testing at 5-year intervals in women of ages 20-70 could achieve greater than 90% reduction in cervical cancer mortality at a cost of 1683 US dollars per LYS, and VIA could achieve 83% reduction at 524 US dollars per LYS. CONCLUSIONS: Well-organized screening programs can reduce cervical cancer mortality in less-developed countries at low costs. These cost-effectiveness data can enhance decision-making about optimal policies for a given setting.

Benefits and costs of using HPV testing to screen for cervical cancer.

CONTEXT: Despite quality assurance standards, Papanicolaou (Pap) test characteristics remain less than optimal. OBJECTIVE: To compare the societal costs and benefits of human papillomavirus (HPV) testing, Pap testing, and their combination to screen for cervical cancer. DESIGN, SETTING, AND POPULATION: A simulation model of neoplasia natural history was used to estimate the societal costs and quality-adjusted life expectancy associated with 18 different general population screening strategies: Pap plus HPV testing, Pap testing alone, and HPV testing alone every 2 or 3 years among hypothetical longitudinal cohorts of US women beginning at age 20 years and continuing to 65 years, 75 years, or death. MAIN OUTCOME MEASURE: Discounted costs per quality-adjusted life-year (QALY) saved of each screening strategy. RESULTS: Maximal savings in lives were achieved by screening every 2 years until death with combined HPV and Pap testing at an incremental cost of $76 183 per QALY compared with Pap testing alone every 2 years. Stopping biennial screening with HPV and Pap testing at age 75 years captures 97.8% of the benefits of lifetime screening at a cost of $70 347 per QALY. Combined biennial HPV and Pap testing to age 65 years captures 86.6% of the benefits achievable by continuing to screen until age 75 years. Human papillomavirus screening alone was equally effective as Pap testing alone at any given screening interval or age of screening cessation but was more costly and therefore was dominated. In sensitivity analyses, HPV testing would be more effective and less costly than Pap testing at a cost threshold of $5 for an HPV test. CONCLUSIONS: Screening with HPV plus Pap tests every 2 years appears to save additional years of life at reasonable costs compared with Pap testing alone. Applying age limits to screening is a viable option to maintain benefits while reducing costs.