0

The full content of Annals is available to subscribers

Subscribe/Learn More  >
Original Research |

Routine Echocardiography Screening for Asymptomatic Left Ventricular Dysfunction in Childhood Cancer Survivors: A Model-Based Estimation of the Clinical and Economic EffectsRoutine Echocardiography Screening for ALVD in Childhood Cancer Survivors

Jennifer M. Yeh, PhD; Anju Nohria, MD; and Lisa Diller, MD
[+] Article and Author Information

From the Harvard School of Public Health, Brigham and Women's Hospital, Dana-Farber Cancer Institute, and Boston Children's Hospital, Boston, Massachusetts.

Grant Support: Dr. Yeh was supported by the National Cancer Institute (grant K07-CA143044).

Disclosures: Disclosures can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M13-2266.

Reproducible Research Statement: Study protocol: Available from Dr. Yeh (e-mail, jyeh@hsph.harvard.edu). Statistical code and data set: Not available.

Requests for Single Reprints: Jennifer M. Yeh, PhD, Center for Health Decision Science, Harvard School of Public Health, 718 Huntington Avenue, Boston, MA 02115; e-mail, jyeh@hsph.harvard.edu.

Current Author Addresses: Dr. Yeh: Center for Health Decision Science, Harvard School of Public Health, 718 Huntington Avenue, Boston, MA 02115.

Dr. Nohria: Brigham and Women's Hospital/Dana-Farber Cancer Institute, 75 Francis Street, Boston, MA 02115.

Dr. Diller: Dana-Farber Cancer Institute/Boston Children's Hospital, 44 Binney Street, Boston, MA 02115.

Author Contributions: Conception and design: J.M. Yeh, A. Nohria, L. Diller.

Analysis and interpretation of the data: J.M. Yeh, A. Nohria, L. Diller.

Drafting of the article: J.M. Yeh, A. Nohria, L. Diller.

Critical revision of the article for important intellectual content: J.M. Yeh, A. Nohria, L. Diller.

Final approval of the article: J.M. Yeh, A. Nohria, L. Diller.

Statistical expertise: J.M. Yeh.

Obtaining of funding: L. Diller.

Administrative, technical, or logistic support: L. Diller.

Collection and assembly of data: J.M. Yeh.


Ann Intern Med. 2014;160(10):661-671. doi:10.7326/M13-2266
Text Size: A A A

Background: Childhood cancer survivors treated with cardiotoxic therapies are recommended to have routine cardiac assessment every 1 to 5 years, but the long-term benefits are uncertain.

Objective: To estimate the cost-effectiveness of routine cardiac assessment to detect asymptomatic left ventricular dysfunction and of angiotensin-converting enzyme inhibitor and β-blocker treatment to reduce congestive heart failure (CHF) incidence in childhood cancer survivors.

Design: Simulation model.

Data Sources: Literature, including data from the Childhood Cancer Survivor Study.

Target Population: Childhood cancer survivors.

Time Horizon: Lifetime.

Perspective: Societal.

Intervention: Interval-based echocardiography assessment every 1, 2, 5, or 10 years, with subsequent angiotensin-converting enzyme inhibitor or β-blocker treatment for patients with positive test results.

Outcome Measures: Lifetime risk for systolic CHF, lifetime costs, quality-adjusted life expectancy, and incremental cost-effectiveness ratios (ICERs).

Results of Base-Case Analysis: The lifetime risk for systolic CHF among 5-year childhood cancer survivors aged 15 years was 18.8% without routine cardiac assessment (average age at onset, 58.8 years). Routine echocardiography reduced lifetime risk for CHF by 2.3% (with assessment every 10 years) to 8.7% (annual assessment). The ICER for assessment every 10 years was $111 600 per quality-adjusted life-year (QALY) compared with no assessment. Assessment every 5 years had an ICER of $117 900 per QALY, and ICERs for more frequent assessment exceeded $165 000 per QALY.

Results of Sensitivity Analysis: Results were sensitive to treatment effectiveness, absolute excess risk for CHF, and asymptomatic left ventricular dysfunction asymptomatic period. The probability that assessment every 10 or 5 years was preferred at a $100 000-per-QALY threshold was 0.33 for the overall cohort.

Limitation: Treatment effectiveness was based on adult data.

Conclusion: Current recommendations for cardiac assessment may reduce CHF incidence, but less frequent assessment may be preferable.

Primary Funding Source: National Cancer Institute.

Figures

Grahic Jump Location
Figure 1.

CHF model diagram.

Health states for the CHF model are depicted. Persons enter the model with no ALVD and face monthly rates of developing ALVD on the basis of age-specific CHF rates. Persons with ALVD face the risk for symptomatic CHF. Once CHF develops, persons face disease-specific death risks. All persons face death risks from background mortality, late recurrence, and noncardiac late effects (including second cancer diagnoses and pulmonary, external, and other causes). Persons are followed throughout their lifetime. ALVD = asymptomatic left ventricular dysfunction; CHF = congestive heart failure.

Grahic Jump Location
Grahic Jump Location
Figure 2.

Cumulative systolic CHF incidence and reduction in lifetime systolic CHF incidence.

CHF = congestive heart failure. A. Cumulative systolic CHF incidence by years since diagnosis for the cohort of childhood cancer survivors (overall and anthracycline subgroups) and general population is shown. Compared with that of the general population, the lifetime relative risk for CHF is 1.3 (range, 1.1 to 1.7) for no anthracycline, 2.1 (range, 1.2 to 3.1) for <250 mg/m2 of anthracycline, and 3.4 (range, 2.2 to 4.4) for ≥250 mg/m2 of anthracycline. B. The reduction in lifetime risk for systolic CHF for the assessment strategies (vs. no assessment) for the overall cohort is shown. The solid line represents the reduction using base-case estimates, and the top and bottom edges of the shaded bars depict the 95% credible interval from probabilistic sensitivity analysis based on 1000 second-order Monte Carlo simulations.

Grahic Jump Location
Grahic Jump Location
Figure 3.

Tornado diagram on sensitivity analysis for select model variables.

Relative influence of select model variables on results for the overall cohort based on 1-way sensitivity analysis. The x-axis shows the effect of changes in selected variables on the ICER of the assessment every 10 y (compared with no assessment). The y-axis shows the selected model variables, with upper and lower bounds used in the sensitivity analysis in parentheses. The shaded bars indicate the ICER variation caused by changes in the value of the indicated variable, whereas all other variables were held constant. ACE = angiotensin-converting enzyme; AER = absolute excess risk; ALVD = asymptomatic left ventricular dysfunction; BB = β-blocker; CHF = congestive heart failure; ICER = incremental cost-effectiveness ratio; QALY = quality-adjusted life-year; RR = relative risk.

* The first number in the range indicates value yielding the lowest ICER; the second indicates value yielding the highest ICER.

† ICER varied from $111 330 to $111 810/QALY gained.

‡ ICER varied from $111 520 to $111 640/QALY gained.

Grahic Jump Location
Grahic Jump Location
Figure 4.

Threshold analysis of the effectiveness of ACE inhibitor and BB treatment for the overall cohort and anthracycline subgroups at a cost-effectiveness threshold of $100 000/QALY.

Optimal strategy based on treatment effectiveness in a cost-effectiveness framework for 2 scenarios: when only 2D echo is available (panel A) and when 2D echo and cMRI are available (panel B). On the x-axis, the RR for CHF associated with treatment is depicted, with 0 indicating complete reduction of risk and 1.0 indicating no treatment effect. The colored regions indicate the range of values over which the specific strategy would be considered optimum given a willingness-to-pay level of $100 000/QALY gained. Black solid and dotted lines indicate the base-case estimate (RR, 0.63 [95% CI, 0.49–0.83]) from the post hoc analysis of the SOLVD prevention trial (28). For example, if only 2D echo is available, annual assessment was the preferred strategy only if treatment reduced CHF risk by 45% (RR, 0.55) for the high-risk subgroup receiving ≥250 mg/m2 of anthracycline; no screening or less frequent screening was preferred at all other values. In contrast, if cMRI is also available, even if treatment completely reduced CHF risk, annual assessment was still not preferred. The 95% CI from the SOLVD prevention trial is shown to depict the uncertainty in treatment effectiveness among adults. The uncertainty range among childhood cancer survivors is likely wider, including lower and negligible benefit (3741). 2D echo = 2-dimensional echocardiography; ACE = angiotensin-converting enzyme; BB = β-blocker; CHF = congestive heart failure; cMRI = cardiac magnetic resonance imaging; QALY = quality-adjusted life-year; RR = relative risk; SOLVD = Studies of Left Ventricular Dysfunction.

Grahic Jump Location
Grahic Jump Location
Appendix Figure.

Threshold analysis of the effectiveness of ACE inhibitor and BB treatment effectiveness for the overall cohort and anthracycline subgroups at a cost-effectiveness threshold of $50 000/QALY.

Optimal strategy based on treatment effectiveness in a cost-effectiveness framework for 2 scenarios: when only 2D echo is available (panel A) and when 2D echo and cMRI are available (panel B). On the x-axis, the relative risk for CHF associated with treatment is depicted, with 0 indicating complete reduction of risk and 1.0 indicating no treatment effect. The colored regions indicate the range of values over which the specific strategy would be considered optimum given a willingness-to-pay level of $50 000/QALY gained. Black solid and dotted lines indicate the base-case estimate (RR, 0.63 [95% CI, 0.49–0.83]) from the post hoc analysis of the SOLVD prevention trial (28). The 95% CI from the SOLVD prevention trial is shown to depict the uncertainty in treatment effectiveness among adults. The uncertainty range among childhood cancer survivors is likely wider, including lower and negligible benefit (3741). 2D echo = 2-dimensional echocardiography; ACE = angiotensin-converting enzyme; BB = β-blocker; CHF = congestive heart failure; cMRI = cardiac magnetic resonance imaging; RR = relative risk; QALY = quality-adjusted life-year; SOLVD = Studies of Left Ventricular Dysfunction.

Grahic Jump Location
Grahic Jump Location
Figure 5.

Cost-effectiveness acceptability curves for the overall cohort and anthracycline subgroups.

Cost-effectiveness acceptability curves, which illustrate the uncertainty surrounding the estimate of ICERs, are depicted for the overall cohort (panel A), the low-risk subgroup receiving <250 mg/m2 of anthracycline (panel B), and the high-risk subgroup receiving ≥250 mg/m2 of anthracycline (panel C). In each panel, the probability that a given strategy is the preferred strategy is depicted across a range of cost-effectiveness thresholds. For example, at a threshold of $100 000/QALY gained, the probability that assessment every 5 y is the preferred strategy is 0.26 for the overall cohort. In contrast, the probability that assessment every 2 y was preferred was 0.57 for the high-risk anthracycline subgroup. Results are based on 1000 second-order Monte Carlo simulations in which model variables were simultaneously varied. The red dashed line indicates the $100 000/QALY threshold commonly used as a benchmark in the United States. QALY = quality-adjusted life-year.

Grahic Jump Location

Tables

References

Letters

NOTE:
Citing articles are presented as examples only. In non-demo SCM6 implementation, integration with CrossRef’s "Cited By" API will populate this tab (http://www.crossref.org/citedby.html).

Comments

Submit a Comment
Submit a Comment

Summary for Patients

Clinical Slide Sets

Terms of Use

The In the Clinic® slide sets are owned and copyrighted by the American College of Physicians (ACP). All text, graphics, trademarks, and other intellectual property incorporated into the slide sets remain the sole and exclusive property of the ACP. The slide sets may be used only by the person who downloads or purchases them and only for the purpose of presenting them during not-for-profit educational activities. Users may incorporate the entire slide set or selected individual slides into their own teaching presentations but may not alter the content of the slides in any way or remove the ACP copyright notice. Users may make print copies for use as hand-outs for the audience the user is personally addressing but may not otherwise reproduce or distribute the slides by any means or media, including but not limited to sending them as e-mail attachments, posting them on Internet or Intranet sites, publishing them in meeting proceedings, or making them available for sale or distribution in any unauthorized form, without the express written permission of the ACP. Unauthorized use of the In the Clinic slide sets will constitute copyright infringement.

Toolkit

Buy Now

to gain full access to the content and tools.

Want to Subscribe?

Learn more about subscription options

Advertisement
Related Articles
Related Point of Care
Topic Collections
PubMed Articles

Buy Now

to gain full access to the content and tools.

Want to Subscribe?

Learn more about subscription options

Forgot your password?
Enter your username and email address. We'll send you a reminder to the email address on record.
(Required)
(Required)