Search tips
Search criteria

Results 1-22 (22)

Clipboard (0)

Select a Filter Below

Year of Publication
1.  Clinical Evaluation of a Multiple-Gene Sequencing Panel for Hereditary Cancer Risk Assessment 
Journal of Clinical Oncology  2014;32(19):2001-2009.
Multiple-gene sequencing is entering practice, but its clinical value is unknown. We evaluated the performance of a customized germline-DNA sequencing panel for cancer-risk assessment in a representative clinical sample.
Patients referred for clinical BRCA1/2 testing from 2002 to 2012 were invited to donate a research blood sample. Samples were frozen at −80° C, and DNA was extracted from them after 1 to 10 years. The entire coding region, exon-intron boundaries, and all known pathogenic variants in other regions were sequenced for 42 genes that had cancer risk associations. Potentially actionable results were disclosed to participants.
In total, 198 women participated in the study: 174 had breast cancer and 57 carried germline BRCA1/2 mutations. BRCA1/2 analysis was fully concordant with prior testing. Sixteen pathogenic variants were identified in ATM, BLM, CDH1, CDKN2A, MUTYH, MLH1, NBN, PRSS1, and SLX4 among 141 women without BRCA1/2 mutations. Fourteen participants carried 15 pathogenic variants, warranting a possible change in care; they were invited for targeted screening recommendations, enabling early detection and removal of a tubular adenoma by colonoscopy. Participants carried an average of 2.1 variants of uncertain significance among 42 genes.
Among women testing negative for BRCA1/2 mutations, multiple-gene sequencing identified 16 potentially pathogenic mutations in other genes (11.4%; 95% CI, 7.0% to 17.7%), of which 15 (10.6%; 95% CI, 6.5% to 16.9%) prompted consideration of a change in care, enabling early detection of a precancerous colon polyp. Additional studies are required to quantify the penetrance of identified mutations and determine clinical utility. However, these results suggest that multiple-gene sequencing may benefit appropriately selected patients.
PMCID: PMC4067941  PMID: 24733792
2.  The MLH1 c.-27C>A and c.85G>T variants are linked to dominantly inherited MLH1 epimutation and are borne on a European ancestral haplotype 
Germline mutations of the DNA mismatch repair genes MLH1, MSH2, MSH6 or PMS2, and deletions affecting the EPCAM gene adjacent to MSH2, underlie Lynch syndrome by predisposing to early-onset colorectal, endometrial and other cancers. An alternative but rare cause of Lynch syndrome is constitutional epimutation of MLH1, whereby promoter methylation and transcriptional silencing of one allele occurs throughout normal tissues. A dominantly transmitted constitutional MLH1 epimutation has been linked to an MLH1 haplotype bearing two single-nucleotide variants, NM_000249.2: c.−27C>A and c.85G>T, in a Caucasian family with Lynch syndrome from Western Australia. Subsequently, a second seemingly unrelated Caucasian Australian case with the same MLH1 haplotype and concomitant epimutation was reported. We now describe three additional, ostensibly unrelated, cancer-affected families of European heritage with this MLH1 haplotype in association with constitutional epimutation, bringing the number of index cases reported to five. Array-based genotyping in four of these families revealed shared haplotypes between individual families that extended across ≤2.6–≤6.4 megabase regions of chromosome 3p, indicating common ancestry. A minimal ≤2.6 megabase founder haplotype common to all four families was identified, which encompassed MLH1 and additional flanking genes and segregated with the MLH1 epimutation in each family. Our findings indicate that the MLH1 c.−27C>A and c.85G>T variants are borne on a European ancestral haplotype and provide conclusive evidence for its pathogenicity via a mechanism of epigenetic silencing of MLH1 within normal tissues. Additional descendants bearing this founder haplotype may exist who are also at high risk of developing Lynch syndrome-related cancers.
PMCID: PMC3992563  PMID: 24084575
Lynch syndrome; MLH1; epimutation; founder haplotype
4.  Preferences for Outcomes Associated with Decisions to Undergo or Forego Genetic Testing for Lynch Syndrome 
Cancer  2012;119(1):215-225.
Current guidelines recommend offering genetic testing for Lynch syndrome to individuals whose tumors suggest this condition and to relatives of affected individuals. Little is known, however, regarding how patients view the prospect of such testing. In addition, data on preferences (utilities) for the potential outcomes of testing decisions for use in cost-effectiveness analyses are lacking.
We elicited time tradeoff utilities for ten potential outcomes of Lynch syndrome testing decisions and three associated cancers from 70 participants representing a range of knowledge about and experiences with Lynch syndrome.
Highest mean utilities were assigned to scenarios in which only the assessor's sibling had Lynch-associated colorectal cancer (ranging from 0.669±0.231 to 0.760±0.220). Utilities assigned to scenarios in which the assessor had Lynch-associated colorectal cancer ranged from 0.605±0.252 to 0.682±0.246, while the lowest mean utilities were assigned to 2 of the general cancer states (0.601±0.238 and 0.593±0.272 for colorectal and ovarian cancer respectively). Only 43% of the sample assigned higher values to undergoing Lynch testing and receiving negative results versus foregoing Lynch testing, while 50% assigned higher values to undergoing rather than foregoing surgery to prevent a subsequent cancer.
Genetic testing for Lynch syndrome, regardless of results, can have profound effects on quality of life; the utilities we collected can be used to incorporate these effects into cost-effectiveness analyses. Importantly, preferences for the potential outcomes of testing vary substantially, calling into question the extent to which patients would avail themselves of such testing if it were offered to them.
PMCID: PMC4356667  PMID: 22786716
Lynch syndrome; hereditary nonpolyposis colorectal cancer; genetic testing; quality of life; utilities; decision making
5.  Cost-effectiveness of colorectal cancer screening in Germany: current endoscopic and fecal testing strategies versus plasma methylated Septin 9 DNA1  
Endoscopy International Open  2014;2(2):E96-E104.
Background and study aims: Colorectal cancer (CRC) screening strategies in Germany include guaiac-based fecal occult blood testing (gFOBT) starting at age 50 and a switch to colonoscopy at age 55 or continued gFOBT testing, but screening utilization is limited. Blood-based biomarkers, such as methylated Septin 9 DNA (mSEPT9), may improve screening rates. We performed a cost-effectiveness analysis of current and emerging CRC screening strategies in Germany.
Methods: Using a validated Markov model, we compared annual gFOBT for ages 50 through 54 followed by biennial testing until age 75 (FOBT) or by colonoscopy at ages 55 and 65 (FOBT/COLO 55,65), substitution of fecal immunochemical testing (FIT) for gFOBT (FIT, FIT/COLO 55,65), and annual or biennial plasma mSEPT9 testing. We also considered persons who utilize only colonoscopy and varied age at colonoscopy utilization.
Results: The current strategies were more effective and less costly than no screening. FIT was more effective and less costly than mSEPT9 testing. FIT/COLO 55,65 cost €12 200 per quality-adjusted life-years gained in comparison with FIT. mSEPT9-based screening was cost-effective in comparison with no screening but was dominated by other cost-saving strategies. Differential screening utilization and adherence greatly affected incremental results between strategies. In probabilistic analyses, FIT was preferred in 49 % and FIT/COLO 55,65 in 47 % of iterations.
Conclusion: Currently available CRC screening strategies in Germany, including hybrid fecal testing/colonoscopy, are likely to be cost-saving. Current strategies appear superior to mSEPT9-based screening. The impact of blood-based biomarkers is likely to depend on utilization and adherence as much as on test performance characteristics and cost.
PMCID: PMC4440365  PMID: 26135268
6.  Cost analysis of a patient navigation system to increase screening colonoscopy adherence among urban minorities 
Cancer  2012;119(3):612-620.
Patient navigation (PN) is being increasingly used to help patients complete screening colonoscopy (SC) to prevent colorectal cancer. At our large urban academic medical center with an open access endoscopy system, we previously demonstrated that PN programs produced a colonoscopy completion rate of 78.5% in a cohort of 503 patients (predominantly African Americans and Latinos with public health insurance). Very little is known about the direct costs of implementing PN programs. The aim of this study was to perform a detailed cost analysis of our PN programs from an institutional perspective.
In two randomized controlled trials, average-risk patients referred for SC by primary care providers were recruited for PN between May 2008 and May 2010. Patients were randomized to one of four PN groups. The cost of PN and net income to the institution were determined in a cost analysis.
Among 395 colonoscopy completers, 53.4% underwent SC alone, 30.1% underwent colonoscopy with biopsy, and 16.5% underwent snare polypectomy. Accounting for the average contribution margins of each procedure type, the total revenue was $95,266.00. The total cost of PN was $14,027.30. Net income was $81,238.70. In a model sample of 1000 patients, we compared net incomes for our completion rate (≈80%), our historical PN program (≈65%), and the national average (≈50%). Our current PN program generated additional net incomes of $35,035.50 and $44,956.00, respectively.
PN among minority patients with mostly public health insurance generated additional income to the institution, due mainly to increased colonoscopy completion rates.
PMCID: PMC3492525  PMID: 22833205
cost analysis; patient navigation; screening colonoscopy; racial disparities; colorectal cancer screening
8.  Strategies to Identify the Lynch Syndrome Among Patients With Colorectal Cancer 
Annals of internal medicine  2011;155(2):69-79.
Testing has been advocated for all persons with newly diagnosed colorectal cancer to identify families with the Lynch syndrome, an autosomal dominant cancer-predisposition syndrome that is a paradigm for personalized medicine.
To estimate the effectiveness and cost-effectiveness of strategies to identify the Lynch syndrome, with attention to sex, age at screening, and differential effects for probands and relatives.
Markov model that incorporated risk for colorectal, endometrial, and ovarian cancers.
Data Sources
Published literature.
Target Population
All persons with newly diagnosed colorectal cancer and their relatives.
Time Horizon
Third-party payer.
Strategies based on clinical criteria, prediction algorithms, tumor testing, or up-front germline mutation testing, followed by tailored screening and risk-reducing surgery.
Outcome Measures
Life-years, cancer cases and deaths, costs, and incremental cost-effectiveness ratios.
Results of Base-Case Analysis
The benefit of all strategies accrued primarily to relatives with a mutation associated with the Lynch syndrome, particularly women, whose life expectancy could increase by approximately 4 years with hysterectomy and salpingo-oophorectomy and adherence to colorectal cancer screening recommendations. At current rates of germline testing, screening, and prophylactic surgery, the strategies reduced deaths from colorectal cancer by 7% to 42% and deaths from endometrial and ovarian cancer by 1% to 6%. Among tumor-testing strategies, immunohistochemistry followed by BRAF mutation testing was preferred, with an incremental cost-effectiveness ratio of $36 200 per life-year gained.
Results of Sensitivity Analysis
The number of relatives tested per proband was a critical determinant of both effectiveness and cost-effectiveness, with testing of 3 to 4 relatives required for most strategies to meet a threshold of $50 000 per life-year gained. Immunohistochemistry followed by BRAF mutation testing was preferred in 59% of iterations in probabilistic sensitivity analysis at a threshold of $100 000 per life-year gained. Screening for the Lynch syndrome with immunohistochemistry followed by BRAF mutation testing only up to age 70 years cost $44 000 per incremental life-year gained compared with screening only up to age 60 years, and screening without an upper age limit cost $88 700 per incremental life-year gained compared with screening only up to age 70 years.
Other types of cancer, uncertain family pedigrees, and genetic variants of unknown significance were not considered.
Widespread colorectal tumor testing to identify families with the Lynch syndrome could yield substantial benefits at acceptable costs, particularly for women with a mutation associated with the Lynch syndrome who begin regular screening and have risk-reducing surgery. The cost-effectiveness of such testing depends on the participation rate among relatives at risk for the Lynch syndrome.
Primary Funding Source
National Institutes of Health.
PMCID: PMC3793257  PMID: 21768580
9.  Economic Evaluation of Targeted Cancer Interventions: Critical Review and Recommendations 
Scientific advances have improved our ability to target cancer interventions to individuals who will benefit most, and spare the risks and costs to those who will derive little benefit or even be harmed. Several approaches are currently used for targeting interventions for cancer risk reduction, screening and treatment, including risk prediction algorithms for identifying high-risk subgroups and diagnostic tests for tumor markers and germline genetic mutations. Economic evaluation can inform decisions about the use of targeted interventions, which may be more costly than traditional strategies. However, assessing the impact of a targeted intervention on costs and health outcomes requires explicit consideration of the method of targeting. Here we describe the importance of this principle by reviewing published cost-effectiveness analyses (CEAs) of targeted interventions in breast cancer. Few studies we identified explicitly evaluated the relationship between the method of targeting, the accuracy of the targeting test and outcomes of the targeted intervention. Those that did found that characteristics of targeting tests had a substantial impact on outcomes. We posit that the method of targeting and the outcomes of a targeted intervention are inextricably linked and recommend that CEAs of targeted interventions explicitly consider costs and outcomes of the method of targeting.
PMCID: PMC3774033  PMID: 21637102
breast cancer; economic analysis; cost-effectiveness analysis; targeted therapy; personalized medicine; BRCA; trastuzumab; gene expression profiling
10.  Disparities in Cancer Screening in Individuals with a Family History of Breast or Colorectal Cancers 
Cancer  2011;118(6):1656-1663.
Understanding racial/ethnic disparities in cancer screening by family history risk could identify critical opportunities for patient and provider interventions tailored to specific racial/ethnic groups. We evaluated whether breast cancer (BC) and colorectal cancer (CRC) disparities varied by family history risk using a large, multiethnic population-based survey.
Using the 2005 California Health Interview Survey, BC and CRC screening were evaluated separately with weighted multivariate regression analyses, and stratified by family history risk. Screening was defined for BC as mammogram within the past 2 years for women aged 40 to 64 years; for CRC, as annual fecal occult blood test, sigmoidoscopy within the past 5 years, or colonoscopy within the past 10 years for adults aged 50 to 64 years.
We found no significant BC screening disparities by race/ethnicity or income in both the family history risk groups. Racial/ethnic disparities were more evident in CRC screening, and the Latino-white gap widened among individuals with family history risk. Among adults with a family history for CRC, magnitude of the Latino-white difference in CRC screening (OR 0.28; 95%CI: 0.11 -0.60) was more substantial than that for individuals with no family history (OR 0.74; 95%CI: 0.59 -0.92).
Knowledge of their family history widened the Latino-white gap in CRC screening among adults. More aggressive interventions that enhance the communication between Latinos and their doctors about family history and cancer risk could reduce the substantial Latino-white screening disparity in Latinos most susceptible to CRC.
PMCID: PMC3262934  PMID: 22009719
family history; cancer screening; cancer disparities; breast cancer; colorectal cancer
11.  Diagnosis, Comorbidities and Management of Irritable Bowel Syndrome in Patients in a Large Health Maintenance Organization 
Irritable bowel syndrome (IBS) imposes significant clinical and economic burdens. We aimed to characterize patterns of practice for patients with IBS who were members of a large health maintenance organization, analyzing point of diagnosis, testing, comorbidities and treatment.
Members of Kaiser Permanente Northern California who were diagnosed with IBS were matched to controls by age, sex, and period of enrollment. We compared rates of testing, comorbidities and interventions.
From 1995 to 2005, IBS was diagnosed in 141,295 patients (mean age 46, SD 17 years; 74% female). Internists made 68% of diagnoses, gastroenterologists 13%, and others 19%. Lower endoscopy did not usually precede IBS diagnosis. Patients with IBS were more likely than controls to have blood, stool, endoscopic and radiologic tests, and to undergo abdominal or pelvic operations (ORs 1.5–10.7, all P<0.0001). Only 2.7% were tested for celiac disease and only 1.8% were eventually diagnosed with inflammatory bowel disease. Chronic pain syndromes, anxiety and depression were more common among IBS patients than controls (ORs 2.7–4.6, all P<0.0001). Many patients with IBS were treated with anxiolytics (61%) and antidepressants (55%). Endoscopic and radiologic testing were most strongly associated with having IBS diagnosed by a gastroenterologist. Psychotropic medication use was most strongly associated with female sex.
In a large, managed care cohort, most diagnoses of IBS were made by generalists, often without endoscopic evaluation. Patients with IBS had consistently higher rates of testing, chronic pain syndromes, psychiatric comorbidity and operations than controls. Most patients with IBS were treated with psychiatric medications.
PMCID: PMC3242893  PMID: 21871250
functional gastrointestinal disorders; therapy; population; epidemiology
12.  Influence of Patient Preferences on the Cost-Effectiveness of Screening for Lynch Syndrome 
Journal of Oncology Practice  2012;8(3 Suppl):e24s-e30s.
This cost-utility analysis reports on the effect of quality of life on the value of screening all new patients with colorectal cancer for Lynch syndrome.
Patients and relatives have varying preferences for genetic testing and interventions related to hereditary cancer syndromes. We examined how the impact of these services on quality of life (QoL) affects the cost-effectiveness of screening for Lynch syndrome among probands newly diagnosed with colorectal cancer and their relatives.
We constructed a state-transition model comparing screening strategies (clinical criteria, prediction algorithms, tumor testing, and upfront germline testing) with no screening to identify Lynch syndrome. The model incorporated individuals' health state utilities after screening, germline testing, and risk-reducing surgeries, with utilities persisting for 12 months in the base case. Outcomes consisted of quality-adjusted life-years (QALYs), costs, and cost per QALY gained. Sensitivity analyses assessed how the duration and magnitude of changes in QoL influenced results.
Multiple screening strategies yielded gains in QALYs at acceptable costs compared with no screening. The preferred strategy—immunohistochemistry of tumors followed by BRAF mutation testing (IHC/BRAF)—cost $59,700 per QALY gained in the base case. The duration and magnitude of decreases in QoL after decisions related to germline testing and surgeries were key determinants of the cost-effectiveness of screening. IHC/BRAF cost > $100,000 per QALY gained when decrements to QoL persisted for 21 months.
Screening for Lynch syndrome in the population is likely to yield long-term gains in life expectancy that outweigh any short-term decreases in QoL, at acceptable costs. Counseling for individuals should aim to mitigate potential negative impact of genetic testing and risk-reducing interventions on QoL.
PMCID: PMC3348599  PMID: 22942831
13.  Cost-Effectiveness of Colorectal Cancer Screening in High Risk Spanish Patients: Use of a Validated Model to Inform Public Policy 
The European Community has made a commitment to colorectal cancer (CRC) screening, but regional considerations may affect the design of national screening programs. We developed a decision analytic model tailored to a pilot screening program for high risk persons in Spain with the aim of informing public policy decisions.
We constructed a decision analytic Markov model based on our validated model of CRC screening that reflected CRC epidemiology and costs in persons with first-degree relatives with CRC in Aragón, Spain, and superimposed colonoscopy every 5 or 10 years from ages 40-80 years. The pilot program’s preliminary clinical results and our modeling results were presented to regional health authorities.
In the model, without screening, 88 CRC cases occurred per 1,000 persons from age 40-85 years. In the base case, screening reduced this by 72-77% and gained 0.12 discounted life-years/person. Screening every 10 years was cost-saving, and screening every 5 years vs. every 10 years cost 7,250 €/life-year gained. Based on these savings, 36-39 €/person/year could go towards operating costs while maintaining a neutral budget. If screening costs doubled, screening remained highly cost-effective, but no longer cost-saving. These results contributed to the health authorities’ decision to expand the pilot program to the entire region in 2009.
Colonoscopic screening of first-degree relatives of persons with CRC may be cost-saving in public systems like Spain’s. Decision analytic modeling tailored to regional considerations can inform public policy decisions.
Tailored decision analytic modeling can inform regional policy decisions on cancer screening.
PMCID: PMC3159034  PMID: 20810603
14.  As Tests Evolve and Costs of Cancer Care Rise: Reappraising Stool-Based Screening for Colorectal Neoplasia 
Colorectal cancer (CRC) screening and treatment are rapidly evolving.
To reappraise stool-based CRC screening in light of changing test performance characteristics, lower test cost, and increasing CRC care costs.
Using a Markov model, we compared fecal DNA testing every 3 years (F-DNA), annual fecal occult blood testing (FOBT) or immunochemical testing (FIT), and colonoscopy every 10 years (COLO).
In the base case, FOBT and FIT gained life-years/person and cost less than no screening. F-DNA version 1.1 at $300 (the current PreGen Plus test) gained 5,323 life-years/100,000 persons at $16,900/life-year gained, and F-DNA version 2 (enhanced test) gained 5,795 life-years/100,000 persons at $15,700/life-year gained vs. no screening. In the base case and most sensitivity analyses, FOBT and FIT were preferred over F-DNA. F-DNA version 2 cost $100,000/life-year gained vs. FIT when per-cycle adherence with FIT was 22%. FIT with excellent adherence was superior to COLO.
As novel biological therapies increase CRC treatment costs, FOBT and FIT could become cost-saving. The cost-effectiveness of F-DNA compared with no screening has improved, but FOBT and FIT are preferred over F-DNA when patient adherence is high. FIT may be comparable to COLO in persons adhering to yearly testing.
PMCID: PMC3170173  PMID: 18248653
15.  Citalopram is not Effective Therapy for Non-Depressed Patients with Irritable Bowel Syndrome 
Background & Aims
Data are conflicting on the benefit of selective serotonin reuptake inhibitors (SSRIs) for patients with irritable bowel syndrome (IBS); the role of visceral sensitivity in IBS pathophysiology is unclear. We assessed the effects of citalopram and the relationships between, symptoms, and quality of life (QOL), and rectal sensitivity in non-depressed patients with IBS.
Patients from primary, secondary and tertiary care centers were randomly assigned to groups given citalopram (20 mg/day for 4 weeks, then 40 mg/day for 4 weeks) or placebo. The study was double masked with concealed allocation. Symptoms were assessed weekly; IBS-QOL and rectal sensation were determined from barostat measurements made at the beginning and end of the study.
Patients that received citalopram did not have a higher rate of adequate relief from IBS symptoms than subjects that received placebo (12/27, 44% vs 15/27, 56% respectively; P=0.59), regardless of IBS subtype. The odds ratio for weekly response to citalopram vs placebo was 0.80 (95% confidence interval [CI] 0.61–1.04). Citalopram did not reduce specific symptoms or increase IBS-QOL scores; it had no effect on rectal compliance and a minimal effect on sensation. Changes in IBS-QOL score and pressure-eliciting pain were correlated (r=0.33, 95% CI 0.03–0.57); changes in symptoms and rectal sensitivity or IBS-QOL scores were not correlated.
Citalopram was not superior to placebo in treating non-depressed IBS patients. Changes in symptoms were not correlated with changes in rectal sensation assessed by barostat; Any benefit of citalopram in non-depressed IBS patients is likely to be modest.
PMCID: PMC2818161  PMID: 19765674
16.  When even people at high risk do not take up colorectal cancer screening 
Gut  2007;56(12):1648-1650.
Despite the most intense efforts by medical professionals, a significant fraction of people who we believe “should” be screened are not being screened
PMCID: PMC2095684  PMID: 17998319
17.  Can calcium chemoprevention of adenoma recurrence substitute or serve as an adjunct for colonoscopic surveillance? 
The aim of this study was to examine the potential cost-effectiveness of calcium chemoprevention post-polypectomy as a substitute or adjunct for surveillance.
We constructed a Markov model of post-polypectomy adenoma recurrence and colorectal cancer (CRC) development, calibrated to data from prospective chemoprevention trials of fiber, calcium, antioxidants, and aspirin. We modeled four scenarios for 50-year-old patients immediately after polypectomy: (i) natural history with no further intervention; (ii) elemental calcium 1,200 mg/day from age 50–80; (iii) surveillance colonoscopy from age 50–80 every 5 years, or 3 years for large adenoma; (iv) calcium + surveillance. Patients were followed up until age 100 or death.
Calcium was cost-effective compared to natural history ($49,900/life-year gained). However, surveillance was significantly more effective than calcium (18.729 versus 18.654 life-years/patient; 76 percent versus 14 percent reduction in CRC incidence) at an incremental cost of $15,900/life-year gained. Calcium + surveillance yielded a very small benefit (0.0003 incremental life-years/patient) compared with surveillance alone, at a substantial incremental cost of $3,090,000/life-year gained.
Post-polypectomy calcium chemoprevention is unlikely to be a reasonable substitute for surveillance. It may be cost-effective in patients unwilling or unable to undergo surveillance.
PMCID: PMC2972652  PMID: 19331713
Calcium; Chemoprevention; Colorectal cancer
18.  Challenges To The Translation Of Genomic Information Into Clinical Practice And Health Policy: Utilization, Preferences, And Economic Value 
It is important to understand how knowledge of genomics can be translated from basic research into clinical practice and health policies. The objective of this paper is to review existing evidence on three key factors in the adoption of personalized medicine – utilization, preferences, and economic value - using two cancer examples: HER2/neu testing and trastuzumab (Herceptin®) and genetic testing for Lynch syndrome. Our findings suggest where further research is needed to build an evidence base addressing utilization of, preferences for, and the potential costs and benefits of personalized medicine. Major challenges include a lack of linked data, the need for relevant research frameworks and methodologies, and the clinical complexities of genomic-based diagnostics and treatment.
PMCID: PMC2910510  PMID: 18535933
Personalized medicine; health policy; health services research; economics; utilization; preferences
19.  Addressing The Challenges Of The Clinical Application Of Pharmacogenetic Testing 
Pharmacogenomics aims to use molecular genetic markers to predict treatment outcome. Indeed within the past decade, there has been a rapid emergence of pharmacogenetic tests to aid clinicians to predict efficacy or toxicity for some drugs. Despite this major advance in therapeutic drug management there remain challenges to the appropriate use of pharmacogenetic tests. We discuss UGT1A1 pharmacogenetic testing to illustrate the knowledge gaps impeding widespread use of pharmacogenetic tests in the clinical setting.
PMCID: PMC2910521  PMID: 19536122
20.  Rate and yield of repeat upper endoscopy in patients with dyspepsia 
AIM: To determine the rate and yield of repeat esophagogastroduodenoscopy (EGD) for dyspepsia in clinical practice, whether second opinions drive its use, and whether it is performed at the expense of colorectal cancer screening.
METHODS: We performed a retrospective cohort study of all patients who underwent repeat EGD for dyspepsia from 1996 to 2006 at the University of California, San Francisco endoscopy service.
RESULTS: Of 24 780 EGDs, 5460 (22%) were performed for dyspepsia in 4873 patients. Of these, 451 patients (9.3%) underwent repeat EGD for dyspepsia at a median 1.7 (interquartile range, 0.8-3.1) years after initial EGD. Significant findings possibly related to dyspepsia were more likely at initial (29%) vs repeat EGD (18%) [odds ratio (OR), 1.45; 95% confidence interval (CI): 1.20-1.75, P < 0.0001], and at repeat EGD if the initial EGD had reported such findings (26%) than if it had not (14%) (OR, 1.32; 95% CI: 1.08-1.62, P = 0.0015). The same endoscopist performed the repeat and initial EGD in 77% of cases. Of patients aged 50 years or older, 286/311 (92%) underwent lower endoscopy.
CONCLUSION: Repeat EGD for dyspepsia occurred at a low but substantial rate, with lower yield than initial EGD. Optimizing endoscopy use remains a public health priority.
PMCID: PMC2877181  PMID: 20503451
Dyspepsia; Esophagogastroduodenoscopy; Health resources; Diagnostic techniques and procedures; Repeat; Treatment outcome
21.  Cost-Effectiveness of Ulcerative Colitis Surveillance in the Setting of 5-Aminosalicylates 
Colorectal cancer (CRC) is a feared complication of chronic ulcerative colitis (UC). Annual endoscopic surveillance is recommended to detect early neoplasia. 5-aminosalicylates (5-ASAs) may prevent some UC-associated CRC. Therefore, in patients prescribed 5-ASAs for maintenance of remission, annual surveillance might be overly burdensome and inefficient. We aimed to determine the ideal frequency of surveillance in patients with UC maintained on 5-ASAs.
We performed systematic reviews of the literature, and created a Markov computer model simulating a cohort of 35 year-old men with chronic UC, followed until age 90. Twenty-two strategies were modeled: Natural History (no 5-ASA or surveillance), surveillance without 5-ASA at intervals of 1 to 10 years, 5-ASA plus surveillance every 1 to 10 years, and 5-ASA alone. The primary outcome was the ideal interval of surveillance in the setting of 5-ASA maintenance, assuming a third-party payer was willing to pay $100,000 for each quality-adjusted life-year (QALY) gained.
In the Natural History strategy, the CRC incidence was 30%. Without 5-ASA, annual surveillance was the ideal strategy, preventing 89% of CRC and costing $69,100 per QALY gained compared to surveillance every 2 years. 5-ASA alone prevented 49% of CRC. In the setting of 5-ASA, surveillance every 3 years was ideal, preventing 87% of CRC. 5-ASA with surveillance every 2 years cost an additional 147,500 per QALY gained, and 5-ASA with annual surveillance cost nearly $1 million additional per QALY gained compared to every 2 years. In Monte Carlo simulations, surveillance every 2 years or less often was ideal in 95% of simulations.
If 5-ASA is efficacious chemoprevention for UC-associated CRC, endoscopic surveillance might be safely performed every 2 years or less often. Such practice could decrease burdens to patients and to endoscopic resources with a minimal decrease in quality-adjusted length of life, since 5-ASA with annual surveillance may cost nearly $1 million per additional QALY gained.
PMCID: PMC2764368  PMID: 19491824
Chemoprevention; Colonic Neoplasms; Decision Support Techniques; Surveillance; Ulcerative Colitis
22.  Rates and Predictors of Colorectal Cancer Screening 
Preventing Chronic Disease  2006;3(4):A117.
Despite widespread recommendations for colorectal cancer screening, the U.S. screening rate is low. The objectives of this study were to describe the rates and predictors of colorectal cancer screening use by examining groups in two categories — 1) those who have ever been screened and 2) those with up-to-date screening — and to assess whether trends and predictors change over time.
We analyzed data from the 2000 and 2003 National Health Interview Surveys about the use of fecal occult blood tests, sigmoidoscopies, and colonoscopies for adults aged 50 years and older and without a history of colorectal cancer (N = 11,574 in 2000 and N = 11,779 in 2003). 
Rates in the 2000 study population of those who have ever been screened for colorectal cancer (53%) had increased in the 2003 study population (55%) as had the rates in the 2003 study population of those with up-to-date colorectal screening (53%) compared with the rates in the 2000 study population (38%). Among those who were ever screened, 76% were up-to-date with screening in 2003, compared with 68% in 2000. There was increased use of colonoscopies but decreased use of fecal occult blood tests and sigmoidoscopies. Individuals were more likely to be up-to-date with screening if they had higher income, higher education, insurance coverage, a usual source of care, and a dental visit in the last year than if these predictors were not evident. Since 2000, these predictors of colorectal cancer screening use have remained stable.
Although there has been relatively limited success in increasing overall screening, it is encouraging that most people in the group of those who have ever been screened are up-to-date with colorectal cancer screening. Predictors for colorectal screening were stable over time despite changes in screening policies and rates. Further research is needed to uncover barriers to colorectal cancer screening.
PMCID: PMC1779281  PMID: 16978492

Results 1-22 (22)