Currently Viewing:
The American Journal of Managed Care July 2014
Managed Care Patients' Preferences, Physician Recommendations, and Colon Cancer Screening
Sarah Hawley, PhD, MPH; Sarah Lillie, PhD; Greg Cooper, MD; and Jennifer Elston Lafata, PhD
Currently Reading
Individual Treatment Effects: Implications for Research, Clinical Practice, and Policy
Jennifer S. Graff, PharmD; Thaddeus Grasela, PharmD, PhD; David O. Meltzer, MD, PhD; and Robert W. Dubois, MD, PhD
Success of Automated Algorithmic Scheduling in an Outpatient Setting
Patrick R. Cronin, MA; and Alexa Boer Kimball, MD, MPH
Drug Plan Design Incentives Among Medicare Prescription Drug Plans
Haiden A. Huskamp, PhD; Nancy L. Keating, MD, MPH; Jesse B. Dalton, MA; Michael E. Chernew, PhD; and Joseph P. Newhouse, PhD
Medicaid Prior Authorization Policies and Imprisonment Among Patients With Schizophrenia
Dana Goldman, PhD; John Fastenau, MPH, RPh; Riad Dirani, PhD; Eric Helland, PhD; Geoff Joyce, PhD; Ryan Conrad, PhD; and Darius Lakdawalla, PhD
Structural Capabilities in Small and Medium-Sized Patient-Centered Medical Homes
Shehnaz Alidina, MPH; Eric C. Schneider, MD, MSc; Sara J. Singer, MBA, PhD; and Meredith B. Rosenthal, PhD
The Underuse of Carotid Interventions in Veterans With Symptomatic Carotid Stenosis
Salomeh Keyhani; Eric Cheng; Susan Ofner; Linda Williams, and Dawn Bravata
Characteristics of Older Adult Physical Activity Program Users
Dori E. Rosenberg, PhD, MPH; Lou Grothaus, MA; and David Arterburn, MD, MPH
Evaluating a Hepatitis C Quality Gap: Missed Opportunities for HCV-Related Care
Yang Liu, MD; Renee H. Lawrence, PhD; Yngve Falck-Ytter, MD; Brook Watts, MD; and Amy A. Hirsch, PharmD
Shifting Cardiovascular Care to Nurses Results in Structured Chronic Care
Elvira Nouwens, MSc; Jan van Lieshout, MD, PhD; Pieter van den Hombergh, MD, PhD; Miranda Laurant, PhD; and Michel Wensing, PhD

Individual Treatment Effects: Implications for Research, Clinical Practice, and Policy

Jennifer S. Graff, PharmD; Thaddeus Grasela, PharmD, PhD; David O. Meltzer, MD, PhD; and Robert W. Dubois, MD, PhD
A framework for researchers, providers, payers, or public health bodies identifies when it is most critical to distinguish between "average" population and individual patient response.
CER will increasingly provide evidence about what treatments work best. For CER to achieve the greatest benefit, we need that evidence for groups of patients as well as for those individuals who may respond differently. We also need to understand the implications of applying population results to particular patients. In some circumstances, population results can and should be applied broadly. In other circumstances, caution is warranted. It is our hope that the framework discussed here begins to address this choice. We hope to encourage discussion about the importance of recognizing when additional research is needed, and about why providers, payers, and policy makers should acknowledge the implications of variation in treatment effect. Doing so should ultimately lead to improvements in health not only for the population as a whole, but also for individual patients like Ms Jones.

Author Affiliations: National Pharmaceutical Council, Washington, DC (JSG, RWD); Cognigen Corporation, Buffalo, NY (TG); Center for Health and the Social Sciences, University of Chicago, Chicago, IL (DOM).

Source of Funding: National Pharmaceutical Council.

Author Disclosures: Drs Graff and DuBois are employed by the Na- tional Pharmaceutical Council, a policy research organization supported by the nation’s major research-based pharmaceutical companies. Dr Grasela is an employee of Cognigen, which provides contract research services in the area of pharmacokinetic and pharmacodynamic modeling. Cognigen also receives consulting fees and fees for public speaking on behalf of client products and projects. Dr Meltzer is a consultant for Patient-Centered Outcomes Research Institute (PCORI) as a member of the methodology committee, and has received research grants for other projects from the National Pharmaceutical Council.

Authorship Information: Concept and design (JSG, RWD, DOM, TG); acquisition of data (JSG, RWD, TG); analysis and interpretation of data (JSG, RWD); drafting of the manuscript (JSG, RWD, DOM, TG); criti- cal revision of the manuscript for important intellectual content (RWD, DOM, TG); obtaining funding (RWD); administrative, technical, or logis- tic support (JSG); supervision (RWD).

Address correspondence to: Jennifer S. Graff, PharmD, National Pharmaceutical Council, 1717 Pennsylvania Ave, Ste 800, Washington, DC 20006. E-mail:
1. Patient Protection and Affordable Care Act; standards related to essential health benefits, actuarial value, and accreditation: a rule by the Health and Human Services Department on 02/25/13. 78 Fed Reg 156.122:12833-12872. 02/25/2013-04084/patient-protection-and-affordable-care-act-standards-related-to-essential-health-benefits-actuarial. Accessed September 27,2013.

2. Gartlehner G, Hansen RA, Morgan LC, et al. Second-generation antidepressants in the pharmacologic treatment of adult depression: an update of the 2007 comparative effectiveness review. (Prepared by the RTI International–University of North Carolina Evidence-based Practice Center, Contract No. 290-2007-10056-I.) AHRQ Publication No. 12-EHC012-EF. Rockville, MD: Agency for Healthcare Research and Quality. Published December 2011. Accessed November 13, 2012.

3. Kent D, Hayward R. When averages hide individual differences in clinical trials. Am Sci. 2007;95(1):60-68.

4. US Government Accountability Office. Public Law 111-148—March 23, 2010: Subtitle D—Patient-Centered Outcomes Research. http:// Accessed September 13, 2013.

5. Patient-Centered Outcomes Research Institute. Funding announcement: improving methods for conducting patient-centered outcomes research. Published November 16, 2012. Updated January 28, 2013. Accessed September 13, 2013.

6. Selby J; Patient-Centered Outcomes Research Institute. Putting the individual patient at the center in clinical research. http://www. Published November 30, 2012.

7. Patient-Centered Outcomes Research Institute. PCORI funding awards: cycle III and inaugural improving methods for conducting PCOR. III-and-Inaugural-Improving-Methods-for-Conducting-PCOR.pdf?2. Accessed September 13, 2013.

8. Epstein AJ, Polsky D,Yang F,Yang L, Groeneveld PW. Coronary revascularization trends in the United States: 2001-2008. JAMA. 2011; 305(17):1769-1776.

9. Kravitz RL, Duan N, Braslow J. Evidence-based medicine, heterogeneity of treatment effects, and the trouble with averages. Milbank Q. 2004;82(4):661-687.

10. Eichler HG, Abadie E, Breckenridge A, et al. Bridging the efficacy-effectiveness gap: a regulator’s perspective on addressing variability of drug response. Nat Rev Drug Discov. 2011;10(7):495-506.

11. Carter GC, Cantrell RA, Zarotsky V, et al. Comprehensive review of factors implicated in the heterogeneity of response in depression. Depress Anxiety. 2012;29(4):340-354.

12. Kent DM, Hayward RA. Limitations of applying summary results of clinical trials to individual patients: the need for risk stratification. JAMA. 2007;298(10):1209-1212.

13. Kent DM, Alsheikh-Ali A, Hayward RA. Competing risk and heterogeneity of treatment effect in clinical trials. Trials. 2008;9:30.

14. Kaplan SH, Billimek J, Sorkin DH, Ngo-Metzger Q, Greenfield S. Who can respond to treatment? identifying patient characteristics related to heterogeneity of treatment effects. Med Care. 2010;48(6 suppl): S9-S16.

15. Nelson JC. Managing treatment-resistant major depression. J Clin Psychiatry. 2003;64(S1):5-12.

16. PhilipsonTJ, Sun E. Blue Pill or Red Pill:The Limits of Comparative Effectiveness Research. Project FDA Report 2011;4.

17. Health policy brief: patient engagement. Health Affairs. Published February 14, 2013. Accessed April 1, 2013.

18. Brett Hauber A, Mohamed AF, Beam C, Medjedovic J, Mauskopf J. Patient preferences and assessment of likely adherence to hepatitis C virus treatment. J Viral Hepat. 2011;18(9):619-627.

19. Veroff D, Marr A, Wennberg DE. Enhanced support for shared decision making reduced costs of care for patients with preference-sensitive conditions. Health Aff (Millwood). 2013;32(2):285-293.

20. Arterburn D, Wellman R, Westbrook E, et al. Introducing decision aids at Group Health was linked to sharply lower hip and knee surgery rates and costs. Health Aff (Millwood). 2013;31(9):2094-2104.

21. Willke RJ, Zheng Z, Subedi P, Althin R, Mullins CD. From concepts, theory, and evidence of heterogeneity of treatment effects to methodological approaches: a primer. BMC Med Res Methodol. 2012;12:185.

22. Hibbard JH, Greene J. What the evidence shows about patient activation: better health outcomes and care experiences; fewer data on costs. Health Aff (Millwood). 2013;32(2):207-214.

23. Gabler NB, Duan N, Liao D, Elmore JG, GaniatsTG, Kravitz RL. Dealing with heterogeneity of treatment effects: is the literature up to the challenge? Trials. 2009;10:43.

24. Kent DM, Rothwell PM, Ioannidis JPA, Altman DG, Hayward RA. Assessing and reporting heterogeneity in treatment effects in clinical trials: a proposal. Trials. 2010;11:85.

25. Sun X, Briel M, Busse JW, et al. Subgroup analysis of trials is rarely easy (SATIRE): a study protocol for a systematic review to characterize the analysis, reporting, and claim of subgroup effects in randomized trials. Trials. 2009;10:101.

26. Patient-Centered Outcomes Research Institute. Public comment draft report of the Patient-Centered Outcomes Research Institute (PCO- RI) Methodology Committee presented on July 23, 2012, and revised thereafter. .pdf. Accessed August 7, 2012.

27. Varadhan R, Segal JB, Boyd CM, Wu AW, Weiss CO. A framework for the analysis of heterogeneity of treatment effect in patient-centered outcomes research. J Clin Epidemiol. 2013;66(8):818-825.

28. Squires D;The Commonwealth Fund. Using comparative effectiveness research to inform policy making. April 2012. http://www. Comparative-Effectiveness-Research-to-Inform-Policymaking.aspx. Accessed September 13, 2013.

29.YapTL,YapWY. Using clinical trial summary results to establish quality measures. JAMA. 2007;298(23):2740-2741.

30. Basu A, Jena AB, PhilipsonTJ.The impact of comparative effectiveness research on health and health care spending. J Health Econ. 2011; 30(4):695-706.

31. Greenfield S, Kravitz R, Duan N, Kaplan SH. Heterogeneity of treatment effects: implications for guidelines, payment, and quality assessment. Am J Med. 2007;120(4, suppl 1):S3-S9.

32. Callahan RH. Creating a new kind of health care community. Forbes. March 3, 2009. patientslikeme-community-database-leadership-clayton-christensen_ disruptor_month.html.

33. Patients Like Me. Major Depressive Disorder symptoms, treat- ments & patient forums. 19-major-depression. Accessed April 1, 2013.

34. Daniels N, Teagarden JR, Sabin JE. An ethical template for pharmacy benefits. Health Aff (Millwood). 2003;22(1):125-137.

35. McLaughlin MJ; HTE Policy Roundtable Panel. Healthcare policy implications of heterogeneity of treatment effects. Am J Med. 2007; 120(4, suppl 1): S32-S35.

36. Della Pasqua O, Santen GW, Danhof M.The missing link between clinical endpoints and drug targets in depression. Trends Pharmacol Sci. 2010;31(4):144-152.

37. Gage BF, van Walraven C, Pearce L, et al. Selecting patients with atrial fibrillation for anticoagulation: stroke risk stratification in patients taking aspirin. Circulation. 2004;110(16):2287-2292.

38. National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology (NCCN guidelines) Guidelines version 2.2012. National Comprehensive Cancer Network. on. Accessed August 7, 2012.

39. Rowland M,TozerTN. Genetics. In: Clinical Pharmacokinetics and Pharmacodynamics: Concepts and Applications. 4th ed. Baltimore, MD: Lippincott Williams & Wilkins; 2011:357-373.

40. Meyer JH. Neuroimaging markers of cellular function in major depressive disorder: implications for therapeutics, personalized medicine, and prevention. Clin PharmacolTher. 2012;91(2):201-214.

41. Adeyemo A, Gerry N, Chen G, et al. A genome-wide association study of hypertension and blood pressure in African Americans. PLoS Genet. 2009;5(7):e1000564.

42. Nallamothu BK, Bates ER, Wang Y, Bradley EH, Krumholz HM. Driving times and distances to hospitals with percutaneous coronary intervention in the United States. Circulation. 2006;113(9):1189-1195.

43.Yildirim-Toruner C, Diamond B. Current and novel therapeutics in the treatment of systemic lupus erythematosus. J Allergy Clin Immunol. 2011;127(2):303-312.

44. Hayes JH, Ollendorf DA, Pearson SD, et al. Active surveillance compared with initial treatment for men with low-risk prostate cancer. JAMA. 2010;304(21):2373-2380.

45. Huang ES, Shook M, Jin L, Chin MH, Meltzer DO.The impact of patient preferences on the cost-effectiveness of intensive glucose control in older patients with new-onset diabetes. Diabetes Care. 2006;29(2): 259-264.
Copyright AJMC 2006-2019 Clinical Care Targeted Communications Group, LLC. All Rights Reserved.
Welcome the the new and improved, the premier managed market network. Tell us about yourself so that we can serve you better.
Sign Up