Implementation and early adaptation of patient-reported outcome measures into an electronic health record: A technical report.

We integrated and optimized patient-reported outcome measures into the electronic health record to provide quantitative, objective data regarding patients' health status, which is important for patient care, payer contracts, and research. With a multidisciplinary team from information technology, clinical informatics, population health, and physician champions, we used formal human-computer interaction techniques and user-centered design to integrate several technology platforms and computerized adaptive testing for the National Institutes of Health Patient-Reported Outcomes Measurement Information System. The patient-reported outcome measure system leverages software frequently used by health systems and provides data for research and clinical care via a mobile-responsive web application using Symfony, with REDCap for configuring assessments and de-identified data storage. The system incorporates Oracle databases and Epic flowsheets. Patients complete patient-reported outcome measures, with data viewable in MyChart and Epic Synopsis Reports. Researchers can access data portals. The highly usable, successful patient-reported outcome measures platform is acceptable to patients and clinicians and achieved 73 percent overall completion rates.

Decision to adopt medical technology: case study of breast cancer radiotherapy techniques.

OBJECTIVE: To understand decision making concerning adoption and nonadoption of accelerated partial breast radiotherapy (RT) prior to long-term randomized trial evidence. METHODS: A total of 36 radiation oncologists and surgeons were recruited through purposive and snowball sampling strategies from September 2010 through January 2013. Semistructured phone interviews were conducted and audio-recorded and lasted 20-45 minutes. Qualitative analysis was conducted using a framework approach, iteratively exploring key concepts and emerging issues raised by subjects. Interviews were transcribed and imported into Atlas.ti v6. Transcripts were independently coded by 3 researchers shortly after each interview, followed by consensus development on each coded transcript. Barriers and facilitators of adoption, practice patterns, and informational/educational sources concerning accelerated partial breast RT were all assessed to determine major themes. RESULTS: Nearly half of physicians were surgeons (47%), and half were radiation oncologists (53%), with 61% overall in urban settings. Twenty-nine of the 36 physicians interviewed used brachytherapy-based partial breast RT. Five major factors were involved in physicians' decisions to adopt accelerated partial breast RT: facilitators encouraging adoption (e.g., enthusiastic colleagues and patient convenience), financial and prestige incentives, pressures to adopt (e.g., potential declines in referrals), judgment concerning acceptable level of scientific evidence, and barriers (e.g., not having appropriate machinery or referral mechanism in place). If technology was adopted, clinical guideline adherence varied. CONCLUSIONS: Technology adoption is based on financial and social pressures, along with often-limited scientific evidence and what seems "best" for patients. For technology adoption and diffusion to be rational and evidence-based, we must encourage appropriate financial payment models to curb use outside of research studies and promote development of additional treatment registries until sufficient evidence is gathered.

Treatment and outcomes in diabetic breast cancer patients.

Effective breast cancer management is more complex with diabetes present and may contribute to poor outcomes. Therefore, we conducted two simultaneous systematic reviews to address the association of diabetes with (1) treatment patterns in breast cancer patients and (2) breast cancer recurrence rates or breast cancer-specific and all-cause mortality. We searched major databases for English language peer-reviewed studies through November 2013, which addressed either of the above research questions, following the preferred reporting items for systematic reviews and meta-analyses (PRISMA) method. Analyses compared treatment patterns or health outcomes for breast cancer subjects with and without diabetes. We used STROBE quality criteria and conducted a random-effects meta-analysis of all-cause mortality. The review yielded 11 publications for question 1 and 26 for question 2, with nine overlapping. Treatment studies showed chemotherapy was less likely in patients with diabetes. Of 22 studies, 21 assessing all-cause mortality indicated a statistically significant increased overall mortality for patients with diabetes (hazard ratios: 0.33-5.40), with meta-analysis of eligible studies indicating a 52 % increased risk. Nine studies assessing breast cancer-specific mortality had inconsistent results, with five showing significantly increased risk for diabetes patients. Results were inconsistent for recurrence and metastases. The majority of studies reported detrimental associations between diabetes and optimal treatment or all-cause mortality among women with breast cancer. Divergence in variable and outcomes inclusion and definitions, potential participation bias in individual studies, and differing analytic methods make inferences difficult. This review illuminates the importance of the impact of diabetes on breast cancer patients and explicitly recognizes that co-management of conditions is necessary to prevent excess morbidity and mortality.

Long-term surveillance mammography and mortality in older women with a history of early stage invasive breast cancer.

Annual surveillance mammograms in older long-term breast cancer survivors are recommended, but this recommendation is based on little evidence and with no guidelines on when to stop. Surveillance mammograms should decrease breast cancer mortality by detecting second breast cancer events at an earlier stage. We examined the association between surveillance mammography beyond 5 years after diagnosis on breast cancer-specific mortality in a cohort of women aged ≥ 65 years diagnosed 1990-1994 with early stage breast cancer. Our cohort included women who survived disease free for ≥ 5 years (N = 1,235) and were followed from year 6 through death, disenrollment, or 15 years after diagnosis. Asymptomatic surveillance mammograms were ascertained through medical record review. We used Cox proportional hazards regression stratified by follow-up year to calculate the association between time-varying surveillance mammography and breast cancer-specific and other-than-breast mortality adjusting for site, stage, primary surgery type, age and time-varying Charlson Comorbidity Index. The majority (85 %) of the 1,235 5-year breast cancer survivors received ≥ 1 surveillance mammogram in years 5-9 (yearly proportions ranged from 48 to 58 %); 82 % of women received ≥ 1 surveillance mammogram in years 10-14. A total of 120 women died of breast cancer and 393 women died from other causes (average follow-up 7.3 years). Multivariable models and lasagna plots suggested a modest reduction in breast cancer-specific mortality with surveillance mammogram receipt in the preceding year (IRR 0.82, 95 % CI 0.56-1.19, p = 0.29); the association with other-cause mortality was 0.95 (95 % CI 0.78-1.17, p = 0.64). Among older breast cancer survivors, surveillance mammography may reduce breast cancer-specific mortality even after 5 years of disease-free survival. Continuing surveillance mammography in older breast cancer survivors likely requires physician-patient discussions similar to those recommended for screening, taking into account comorbid conditions and life-expectancy.

Cost effectiveness of new breast cancer radiotherapy technologies in diverse populations.

Accelerated partial breast radiotherapy (RT) strategies (3-D conformal external-beam RT (3-D CRT) and brachytherapy with balloon catheter) reduce time and transportation burdens of whole breast RT for breast cancer. Long-term clinical trial evidence is unavailable for accelerated modalities, but uncertainty might be acceptable for patients likely to receive suboptimal whole breast RT. The objective of this study is to assess the cost effectiveness of accelerated partial breast RT compared to on-time and delayed whole breast RT. The design used in this study is decision analytic Markov model. The data sources are published literature; and national/federal sources. The target population of this study is a hypothetical cohort of 60 years old women previously treated with breast-conserving surgery for node-negative, estrogen receptor-positive breast cancer with tumors <1 cm. The time horizon is 15 years, and the perspective is societal. The interventions are whole breast RT, 3-D CRT, and brachytherapy breast irradiation. The outcome measures are costs (2008 US$), quality-adjusted life years (QALYs), and incremental cost-effectiveness ratios. The base-case results were: 3-D CRT was the preferred strategy, costing on average $10,800 and yielding 11.21 QALYs. On-time whole breast RT costs $368,000/QALY compared to 3-D CRT, above the $100,000/QALY WTP threshold. 3-D CRT was also preferred over delayed whole breast RT. Brachytherapy was never preferred. Sensitivity analysis indicated that the results were sensitive to the rate of recurrence outside the initial tumor quadrant ("elsewhere failure") in one-way analysis. Probabilistic sensitivity analysis indicated that results were sensitive to parameter uncertainty, and that the elsewhere-failure rate and treatment preferences may drive results. The limitation of this study is that efficacy estimates are derived from studies that may not fully represent the population modeled. As a conclusion, 3-D CRT was preferred to whole breast RT and for women likely to delay RT, indicating that 3-D CRT could be targeted more efficiently before randomized trial evidence.

Structural estimates of treatment effects on outcomes using retrospective data: an application to ductal carcinoma in situ.

Analysis of observational cohort data is subject to bias from unobservable risk selection. The authors compared econometric models and treatment effectiveness estimates using the linked Surveillance, Epidemiology, and End Results (SEER)-Medicare claims data for women diagnosed with ductal carcinoma in situ. Treatment effectiveness estimates for mastectomy and breast-conserving surgery (BCS) with or without radiotherapy were compared using three different models: simultaneous-equations model, discrete-time survival model with unobserved heterogeneity (frailty), and proportional hazards model. Overall trends in disease-free survival (DFS), or time to first subsequent breast event, by treatment are similar regardless of the model, with mastectomy yielding the highest DFS over 8 years of follow-up, followed by BCS with radiotherapy, and then BCS alone. Absolute rates and direction of bias varied substantially by treatment strategy. DFS was underestimated by single-equation and frailty models compared with the simultaneous-equations model and randomized controlled trial results for BCS with radiotherapy and overestimated for BCS alone.

Delayed radiotherapy for breast cancer patients in integrated delivery systems.

OBJECTIVE: To identify factors associated with delayed radiotherapy (RT) in older women with early-stage breast cancer. METHODS: We studied 541 women age >or=65 years diagnosed with early-stage breast cancer in 1990-1994 at 5 integrated healthcare delivery systems and treated with breast-conserving surgery and RT, but not chemotherapy. We examined whether demographic, tumor, or treatment characteristics were associated with RT delays of >8 weeks postsurgery using chi(2) tests and multivariable logistic regression. RESULTS: Seventy-six women (14%) had delayed RT, with a median delay of 14 weeks. Even though they had insurance and access to care, nonwhite and Hispanic women were much more likely than white women to have delayed RT (odds ratio = 3.3; 95% confidence interval = 1.7, 10) in multivariable analyses that controlled for demographic and clinical variables. CONCLUSIONS: Timely RT should be facilitated through physician and patient education, navigation, and notification programs to improve quality of care. Queues for RT appointments should be evaluated on an ongoing basis to ensure adequate access. Future research should examine modifiable barriers to RT timeliness and whether delays impact long-term outcomes.

Referral, receipt, and completion of chemotherapy in patients with early-stage breast cancer older than 65 years and at high risk of breast cancer recurrence.

PURPOSE: Some women with early-stage breast cancer are at higher risk of recurrence and can benefit from chemotherapy. We describe patterns of referral, receipt, and completion of chemotherapy among older women at high risk of recurrence. PATIENTS AND METHODS: A total of 2,124 women age 65 years or older who were diagnosed with early-stage breast cancer between 1990 and 1994 and 1996 to 1999 were included; 1,090 of these were at high risk of recurrence. We reviewed medical records to categorize chemotherapy outcomes as follows: did not discuss or were not referred to a medical oncologist (n = 133); discussed and/or referred to a medical oncologist but received no chemotherapy (n = 742); received an incomplete chemotherapy course (n = 29), or received a completed chemotherapy course (n = 186). RESULTS: Overall, 19.7% of high-risk women received any chemotherapy, and 86.5% of these women completed their chemotherapy courses. Just greater than 10% of high-risk women did not have a discussion about chemotherapy as part of breast cancer treatment documented in the medical record; these women also received fewer diagnostic assessments of their initial tumors. CONCLUSION: Individuals who receive chemotherapy for early-stage breast cancer are a select subgroup of patients at high risk of recurrence. This study identifies characteristics of women who were referred for and who received chemotherapy, and this study plays an important role in understanding generalizability of studies that examine chemotherapy treatment effectiveness. Outcomes after breast cancer could continue to be improved with increased receipt of chemotherapy among older women at high risk of breast cancer recurrence.

Cost effectiveness of pharmacogenetic testing for uridine diphosphate glucuronosyltransferase 1A1 before irinotecan administration for metastatic colorectal cancer.

BACKGROUND: The objective of this study was to examine the cost effectiveness of using a pharmacogenetic test for uridine diphosphate glycosyltransferase 1A1*28 (UGT1A1*28) variant homozygosity before administering irinotecan to patients with metastatic colorectal cancer. METHODS: A decision-analytic model from the Medicare payer perspective followed hypothetical patients who were treated with combined 5-fluorouracil, leucovorin, and irinotecan. Under usual care, patients received a full dose of irinotecan. With genetic testing, irinotecan dosage was reduced 25% in homozygotes with the UGT1A1*28 variant allele. Test performance, chemotherapy toxicity, and quality-of-life weights were derived from clinical literature and product labels, and costs were derived from 2007 Medicare fee schedules. Chemotherapy efficacy after dose reduction, adverse event risk, and other parameters were varied in 1-way and probabilistic sensitivity analyses. The authors also calculated the value of investing in further studies of chemotherapy efficacy after homozygote dose reductions. RESULTS: Pretreatment genetic testing costs less ($272 savings per patient tested) and yields slightly improved quality-adjusted life expectancy (0.1 quality-adjusted day per patient tested; approximately 2 quality-adjusted hours). Results depended on treatment efficacy but not adverse event risk assumptions. The results indicated that testing would avoid 84 cases of severe neutropenia, including 4.4 deaths. At a threshold of $100,000 per quality-adjusted life year, the therapeutic efficacy of irinotecan in homozygotes after dose reduction had to be > or =98.4% of full-dose efficacy for genetic testing to remain preferred. Future studies to determine whether this efficacy level can be achieved have an economic value of $22 million. CONCLUSIONS: The current results indicated that pharmacogenetic testing for UGT1A1*28 variant homozygosity may be cost effective, but only if irinotecan dose reduction in homozygotes does not reduce efficacy. Future studies to evaluate reduced-dose efficacy in homozygotes should be considered.

Effect of socioeconomic factors on long-term mortality in men with clinically localized prostate cancer.

OBJECTIVES: To examine the effect of socioeconomic factors on survival in black and white patients with local or regional prostate cancer. METHODS: All cases (n = 2046) of clinically localized prostate cancer diagnosed from 1990 to 2000 at the Henry Ford Health System and the Henry Ford Medical Group, equal access health centers, were included. Data on the stage, grade, age at diagnosis, socioeconomic status, treatment given, comorbidities, and vital statistics were gathered from the Henry Ford Medical Group tumor registry and computerized databases, pathologic reports, patient charts, Surveillance, Epidemiology, and End Results database, and the national death registry. The endpoints were the overall and cancer-specific survival. Survival was calculated using Cox proportional hazards regression models. RESULTS: Of the 2046 cases, 1243 were white and 803 were black. Black patients were more likely to have lower incomes, a greater baseline prostate-specific antigen level, and greater comorbidities. They were also more likely to undergo radiotherapy and less likely to undergo radical prostatectomy. Univariate analysis, with white race as the baseline hazard, showed that black patients had significantly increased cancer-specific (hazard ratio [HR] 1.47, 95% confidence interval [CI] 1.01-2.13) and overall (HR 1.29, 95% CI 1.09-1.53) mortality. However, adjusting for insurance status and income on multivariate analysis revealed no significant differences in cancer-specific (HR 1.04, 95% CI 0.66-1.64) and overall (HR 0.96, 95% CI 0.78-1.18) survival. CONCLUSIONS: In this cohort, socioeconomic factors were sufficient to explain the disparity in survival between white and black patients. Survival differences disappeared after adjusting for income status on multivariate analysis.

Correlates and effect of suboptimal radiotherapy in women with ductal carcinoma in situ or early invasive breast cancer.

BACKGROUND: The study aimed to identify factors associated with less-than-optimal radiotherapy (RT) and its impact on disease-free survival in women aged 66+ years diagnosed with stage I breast cancer or ductal carcinoma in situ (DCIS). METHODS: The subjects were women diagnosed from 1991 to 1999 in the linked Surveillance, Epidemiology, and End Results (SEER)-Medicare database who underwent breast-conserving surgery and RT within 12 months postdiagnosis. The authors conducted descriptive and multivariate survival analyses, and considered age, race, poverty, marital status, comorbidity indices, rural/urban, radiation oncologist density, comedo necrosis histology (DCIS only), chemotherapy receipt (stage I only), and RT completion (3+ weeks of treatment) and delay (8+ weeks postsurgery without chemotherapy; 4+ weeks postchemotherapy). RESULTS: Of 7791 subjects, 16% experienced RT delay, and 3% had incomplete RT. Subjects with stage I disease who were more likely to delay RT were of black race (odds ratio [OR], 1.56; 95% confidence interval [CI], 1.17-2.08), whereas women in areas of high radiation oncologist density were less likely to delay (OR, 0.73; 95% CI, 0.66-0.81). Those living in high poverty areas were less likely to complete RT (P < .03), as were those undergoing chemotherapy (OR, 1.82; 95% CI, 1.15-2.88). Stage I breast cancer patients with delayed RT were more likely to experience a subsequent breast event (OR, 1.14; 95% CI, 1.00-1.30), and those with incomplete RT had a higher rate of overall mortality (OR, 1.32; 95% CI, 1.06-1.63). Factors associated with lower subsequent breast events included older age, lower poverty, and being married. RT delays of 12+ weeks (or 8+ weeks postchemotherapy) had a strongly negative impact on subsequent events (OR, 3.94; 95% CI, 2.51-6.17 for DCIS; OR, 2.77; 95% CI, 1.84-2.59 for stage I). CONCLUSIONS: RT should be facilitated to ensure completion and timeliness, especially for early invasive breast cancer patients.

Variations in treatment for ductal carcinoma in situ in elderly women.

OBJECTIVE: The objective of this study is to quantify variation and variability in treatment of ductal carcinoma in situ (DCIS) over time and across registries of the Surveillance, Epidemiology, and End Results (SEER) program; to assess diffusion of treatments (breast-conserving surgery [BCS], BCS with radiotherapy, and mastectomy); and to identify correlates of treatment choice. DATA: The linked SEER-Medicare database from 1991 to 1996 includes 2701 women aged 65 and older diagnosed with unilateral DCIS. 1990 census data provide socioeconomic variables at the zip-code level, and the 1999 Dartmouth Atlas of Health Care provides number of radiation oncologists. STUDY DESIGN: Bivariate and multivariate analyses of retrospective cohort data assess factors that explain treatment choice. The multivariate model includes controls for comorbidity, marital status, age, race, education, poverty, rural, and radiation oncologists per 100,000 population. Chi-squared tests assess differences in treatment rates by registry and by year. Diffusion of treatments is analyzed by predicting yearly mean treatment rates and yearly variation in treatment rates across geographic areas and over time. RESULTS: There are significant geographic and temporal differences in treatment rates for DCIS with increasing use of BCS alone. Treatment choice is explained by SEER registry, diagnosis year, marital status, race, age, urban/rural status, educational attainment, and number of radiation oncologists. Variability in treatment of DCIS is increasing during the study period. CONCLUSIONS: Findings indicate that diagnosis year and socioeconomic factors explain treatment choice for DCIS, but unexplained variation at the geographic-region level remains. Increasing variability in treatment implies continued uncertainty about optimal treatment of DCIS.

How often do sensitivity analyses for economic parameters change cost-utility analysis conclusions?

BACKGROUND: There is limited evidence about the extent to which sensitivity analysis has been used in the cost-effectiveness literature. Sensitivity analyses for health-related QOL (HR-QOL), cost and discount rate economic parameters are of particular interest because they measure the effects of methodological and estimation uncertainties. AIM: To investigate the use of sensitivity analyses in the pharmaceutical cost-utility literature in order to test whether a change in economic parameters could result in a different conclusion regarding the cost effectiveness of the intervention analysed. METHODS: Cost-utility analyses of pharmaceuticals identified in a prior comprehensive audit (70 articles) were reviewed and further audited. For each base case for which sensitivity analyses were reported (n = 122), up to two sensitivity analyses for HR-QOL (n = 133), cost (n = 99), and discount rate (n = 128) were examined. Article mentions of thresholds for acceptable cost-utility ratios were recorded (total 36). Cost-utility ratios were denominated in US dollars for the year reported in each of the original articles in order to determine whether a different conclusion would have been indicated at the time the article was published. Quality ratings from the original audit for articles where sensitivity analysis results crossed the cost-utility ratio threshold above the base-case result were compared with those that did not. RESULTS: The most frequently mentioned cost-utility thresholds were $US20,000/QALY, $US50,000/QALY, and $US100,000/QALY. The proportions of sensitivity analyses reporting quantitative results that crossed the threshold above the base-case results (or where the sensitivity analysis result was dominated) were 31% for HR-QOL sensitivity analyses, 20% for cost-sensitivity analyses, and 15% for discount-rate sensitivity analyses. Almost half of the discount-rate sensitivity analyses did not report quantitative results. Articles that reported sensitivity analyses where results crossed the cost-utility threshold above the base-case results (n = 25) were of somewhat higher quality, and were more likely to justify their sensitivity analysis parameters, than those that did not (n = 45), but the overall quality rating was only moderate. CONCLUSIONS: Sensitivity analyses for economic parameters are widely reported and often identify whether choosing different assumptions leads to a different conclusion regarding cost effectiveness. Changes in HR-QOL and cost parameters should be used to test alternative guideline recommendations when there is uncertainty regarding these parameters. Changes in discount rates less frequently produce results that would change the conclusion about cost effectiveness. Improving the overall quality of published studies and describing the justifications for parameter ranges would allow more meaningful conclusions to be drawn from sensitivity analyses.