REFERENCES

ACCORD Study Group, W. C. Cushman, G. W. Evans, R. P. Byington, D. C. Goff, Jr., R. H. Grimm, Jr., J. A. Cutler, D. G. Simons-Morton, J. N. Basile, M. A. Corson, J. L. Probstfield, L. Katz, K. A. Peterson, W. T. Friedewald, J. B. Buse, J. T. Bigger, H. C. Gerstein, and F. Ismail-Beigi. 2010. Effects of intensive blood pressure control in type 2 diabetes mellitus. The New England Journal of Medicine 362(17):1575–1585.

Athey, S., and G. Imbens. 2016. Recursive partitioning for heterogeneous causal effects. Proceedings of the National Academy of Sciences 113(27):7353–7360.

Basu, S., J. S. Yudkin, J. B. Sussman, C. Millett, and R. A. Hayward. 2016. Alternative strategies to achieve cardiovascular mortality goals in China and India: A microsimulation of target-versus risk-based blood pressure treatment. Circulation 133(9):840–848.

Basu, S., J. B. Sussman, J. Rigdon, L. Steimle, B. T. Denton, and R. Hayward. 2017. Benefit and harm of intensive blood pressure treatment: Derivation and validation of risk models using data from SPRINT and ACCORD trials. PLoS Medicine 14(10):e1002410.

Calfee, C. S., K. Delucchi, P. E. Parsons, B. T. Thompson, L. B. Ware, M. A. Matthay, and the NHLBI ARDS Network. 2014. Subphenotypes in acute respiratory distress syndrome: Latent class analysis of data from two randomised controlled trials. Lancet Respiratory Medicine 2(8):611–620.

Carey, L. A., and E. P. Winer. 2016. I-SPY 2—Toward more rapid progress in breast cancer treatment. The New England Journal of Medicine 375(1):83–84.

Carson, P., S. Ziesche, G. Johnson, and J. N. Cohn. 1999. Racial differences in response to therapy for heart failure: Analysis of the vasodilator-heart failure trials. Journal of Cardiac Failure 5(3):178–187.

Chassin, M. R., J. Kosecoff, D. H. Solomon, and R. H. Brook. 1987. How coronary angiography is used. Clinical determinants of appropriateness. JAMA 258(18):2543–2547.

Cohn, J. N., D. G. Archibald, S. Ziesche, J. A. Franciosa, W. E. Harston, F. E. Tristani, W. B. Dunkman, W. Jacobs, G. S. Francis, K. H. Flohr, S. Goldman, F. R. Cobb, P. M. Shah, R. Saunders, R. D. Fletcher, H. S. Loeb, V. C. Hughes, and B. Baker. 1986. Effect of vasodilator therapy on mortality in chronic congestive heart failure Results of a Veterans Administration Cooperative Study. New England Journal of Medicine 314(24):1547–1552.

Cohn, J. N., G. Johnson, S. Ziesche, F. Cobb, G. S. Francis, F. Tristani, R. Smith, W. B. Dunkman, H. Loeb, M. Wong, G. Bhat, S. Goldman, R. D. Fletcher, J. Doherty, C. V. Hughes, P. Carson, G. Cintron, R. Shabetai, and C. Haakenson. 1991. A comparison of enalapril with hydralazin-isosorbide dinitrate in the treatment of chronic congestive heart failure. The New England Journal of Medicine 325(5):303–310.

Decker, C., L. Garavalia, B. Garavalia, E. Gialde, R. W. Yeh, J. Spertus, and A. K. Chhatriwalla. 2016. Understanding physician-level barriers to the use of individualized risk estimates in percutaneous coronary intervention. American Heart Journal 178:190–197. https://doi.org/10.1016/j.ahj.2016.03.027.

Frangakis, C. E., and D. B. Rubin. 2002. Principal stratification in causal inference. Biometrics 58(1):21–29.

Friedman, R. A. 2015. To treat depression, drugs or therapy? The New York Times, January 8.

Gandhi, T. K., S. N. Weingart, J. Borus, A. C. Seger, J. Peterson, E. Burdick, D. L. Seger, K. Shu, F. Federico, L. L. Leape, and D. W. Bates. 2003. Adverse drug events in ambulatory care. The New England Journal of Medicine 348:1556–1564.

Goldstein, D. B. 2009. Common genetic variation and human traits. The New England Journal of Medicine 360(17):1696–1698.

Holtzman, N., and T. Marteau. 2000. Will genetics revolutionize medicine? The New England Journal of Medicine 343(2):141–144.

Hulot, J. S., A. Bura, E. Villard, M. Azizi, V. Remones, C. Goyenvalle, M. Aiach, P. Lechat, and P. Gaussem. 2006. Cytochrome P450 2C19 loss-of-function polymorphism is a major determinant of clopidogrel responsiveness in healthy subjects. Blood 108(7):2244–2247. doi: 10.1182/blood-2006-04-013052.

Ioannidis, J. P. 2009. Prediction of cardiovascular disease outcomes and established cardiovascular risk factors by genome-wide association markers. Circulation: Cardiovascular Genetics 2(1):7–15.

Janes, H., M. S. Pepe, L. S. McShane, D. J. Sargeant, and P. J. Heagerty. 2015. The fundamental difficulty with evaluating the accuracy of biomarkers for guiding treatment. Journal of the National Cancer Institute 107(8):pii:djv157.

Janssens, A. C., and C. M. van Duijn. 2008. Genome-based prediction of common diseases: Advances and prospects. Human Molecular Genetics 17(R2):R166–R173.

Janssens, A. C., M. C. Pardo, E. W. Steyerberg, and C. M. van Duijn. 2004. Revisiting the clinical validity of multiplex genetic testing in complex diseases. American Journal of Human Genetics 74(3):585–589.

Kahneman, D., P. Slovic, and A. Tversky. 1982. Judgment under uncertainty: Heuristics and biases. First edition. New York: Cambridge University Press.

Karmali, K. N., D. M. Lloyd-Jones, J. van der Leeuw, D. C. Goff, Jr., S. Yusuf, A. Zanchetti, P. Glasziou, R. Jackson, M. Woodward, A. Rodgers, B. C. Neal, E. Berge, K. Teo, B. R. Davis, J. Chalmers, C. Pepine, K. Rahimi, and J. Sundström. 2018. Blood pressure-lowering treatment strategies based on cardiovascular risk versus blood pressure: A meta-analysis of individual participant data. PLoS Medicine 15(3):e1002538. doi: 10.1371/journal.pmed.1002538.

Kent, D. M., and R. D. Hayward. 2007. Limitations of applying summary results of clinical trials to individual patients: The need for risk stratification. JAMA 298(10):1209–1212.

Kent, D. M., C. H. Schmid, J. Lau, and H. P. Selker. 2002. Is primary angioplasty for some as good as primary angioplasty for all? Modeling across trials and individual patients. Journal of General Internal Medicine 17:887–894.

Kent, D. M., P. M. Rothwell, J. P. Ioannidis, D. G. Altman, and R. A. Hayward. 2010. Assessing and reporting heterogeneity in treatment effects in clinical trials: A proposal. Trials 11:85.

Khera, A. V., M. Chaffin, K. Aragam, C. A. Emdin, D. Klarin, M. Haas, C. Roselli, P. Natarajan, and S. Kathiresan. 2018. Genome-wide polygenic score to identify a monogenic risk-equivalent for coronary disease. Nature Genetics 50:1219–1224.

Knaus, W. A., D. P. Wagner, E. A. Draper, J. E. Zimmerman, M. Bergner, P. G. Bastos, C. A. Sirio, D. J. Murphy, T. Lotring, A. Damiano, and F. E. Harrell, Jr. 1991. The APACHE III prognostic system: Risk prediction of hospital mortality for critically ill hospitalized adults. Chest 100(6):1619–1636.

Kozminski, M. A., J. T. Wei, J. Nelson, and D. M. Kent. 2015. Baseline characteristics predict risk of progression and response to combined medical therapy for benign prostatic hyperplasia (BPH). BJU International 115(2):308–316.

Kravitz, R. L., N. Duan, and J. Braslow. 2004. Evidence-based medicine, heterogeneity of treatment effects, and the trouble with averages. Milbank Quarterly 82(4):661–687.

Lango, H., the UK Type 2 Diabetes Genetics Consortium, C. Palmer, A. Morris, E. Ziggini, A. Hattersley, M. McCarthy, T. Frayling, and M. Weedon. 2008. Assessing the combined impact of 18 common genetic variants of modest effect sizes on type 2 diabetes risk. Diabetes 57(11):3129–3135.

Manolio, T. A., F. S. Collins, N. J. Cox, D. B. Goldstein, L. A. Hindorff, D. J. Hunter, M. I. McCarthy, E. M. Ramos, L. R. Cardon, A. Chakravarti, J. H. Cho, A. E. Guttmacher, A. Kong, L. Kruglyak, E. Mardis, C. N. Rotimi, M. Slatkin, D. Valle, A. S. Whittemore, M. Boehnke, A. G. Clark, E. E. Eichler, G. Gibson, J. L. Haines, T. F. C. Mackay, S. A. McCarroll, and P. M. Visscher. 2009. Finding the missing heritability of complex diseases. Nature 461(7265):747–753.

McGrath, C. L., M. E. Kelley, P. E. Holtzheimer III, B. W. Dunlop, W. E. Craighead, A. Franco, C. Craddock, and H. Mayberg. 2013. Toward a neuroimaging treatment selection for major depressive disorder. JAMA Psychiatry 70(8):821–829.

Meehl, P. E. 2013. Clinical versus statistical precision: A theoretical analysis and a review of the evidence. Brattleboro, VT: Echo Point Books & Media.

Newman, W. G., K. Payne, K. Tricker, S. Roberts, R. Elltiott, E. Fargher, S. Pushpakom, J. E. Alder, G. P. Sidgwick, D. Payne, R. A. Elliott, M. Heise, R. Elles, S. C. Ramsden, J. Andrews, J. B. Houston, F. Qasim, J. Shaffer, C. E. M. Griffiths, D. W. Ray, I. Bruce, W. E. R. Ollier, and the TARGET study recruitment team. 2011. A pragmatic randomized controlled trial of thiopurine methyltransferase genotyping prior to azathioprine treatment: The TARGET study. Pharmacogenomics 12(6):815–826.

Park, J. W., M. C. Liu, D. Yee, C. Yau, L. J. van’tVeer, Fr. Symmans, M. Paoloni, J. Perlmutter, N. M. Hylton, M. Hogarth, A. DeMichele, M. B. Buxton, A. J. Chien, A. M. Wallace, J. C. Boughey, T. C. Haddad, S. Y. Chui, K. A. Kemmer, H. G. Kaplan, C. Isaacs, R. Nanda, D. Tripathy, K. S. Albain, K. K. Edmiston, A. D. Elias, D. W. Northfelt, L. Pusztai, S. L. Moulder, J. E. Lang, R. K. Viscusi, D. M. Euhus, B. B. Haley, Q. J. Khan, W. C. Wood, M. Melisko, R. Schwab, T. Helsten, J. Lyandres, S. E. Davis, G. L. Hirst, A. Sanil, L. J. Esserman, and D. A. Berry for the I-SPY 2 Investigators. 2016. Adaptive randomization of neratinib in early breast cancer. The New England Journal of Medicine 375:11–22.

Pharoah, P. D., A. Antoniou, M. Bobrow, R. L. Zimmern, D. F. Easton, and B. A. Ponder. 2002. Polygenic susceptibility to breast cancer and implications for prevention. Nature Genetics 31(1):33–36.

Qian, M., and S. A. Murphy. 2011. Performance guarantees for individualized treatment rules. Annals of Statistics 39(2):1180–1210.

Rothwell, P. M., Z. Mehta, S. C. Howard, S. A. Gutnikov, and C. P. Warlow. 2005. Treating individuals 3: From subgroups to individuals: General principles and the example of carotid endarterectomy. Lancet 365(9455):256–265.

Rugo, H. S., O. I. Olopade, A. DeMichele, C. Yau, L. J. van’t Veer, M. B. Buxton, M. Hogarth, N. M. Hylton, M. Paoloni, J. Perlmutter, W. F. Symmans, D. Yee, A. J. Chien, A. M. Wallace, H. G. Kaplan, J. C. Boughey, T. C. Haddad, K. S. Albain, M. C. Liu, C. Isaacs, Q. J. Khan, J. E. Lang, R. K. Viscusi, L. Pusztai, S. L.

Moulder, S. Y. Chui, K. A. Kemmer, A. D. Elias, K. K. Edmiston, D. M. Euhus, B. B. Haley, R. Nanda, D. W. Northfelt, D. Tripathy, W. C. Wood, C. Ewing, R. Schwab, J. Lyandres, S. E. Davis, G. L. Hirst, A. Sanil, D. A. Berry, and L. J. Esserman. 2016. Adaptive randomization of veliparib-carboplatin treatment in breast cancer. The New England Journal of Medicine 375(1):23–34.

Simon, R. 2015. Sensitivity, specificity, PPV, NPV for predictive biomarkers. Journal of the National Cancer Institute 107(8):pii:djv153.

Spertus, J., C. Decker, E. Gialde, P. Jones, E. McNulty, R. Bach, and A. Chhatriwalla. 2015. Precision medicine to improve use of bleeding avoidance strategies and reduce bleeding in patients undergoing percutaneous coronary intervention: Prospective cohort study before and after implementation of personalized bleeding risks. The BMJ 350:h1302.

SPRINT Research Group, J. T. Wright, Jr, J. D. Williamson, P. K. Whelton, J. K. Snyder, K. M. Sink, M. V. Rocco, D. M. Reboussin, M. Rahman, S. Oparil, C. E. Lewis, P. L. Kimmel, K. C. Johnson, D. C. Goff, Jr, L. J. Fine, J. A. Cutler, W. C. Cushman, A. K. Cheung, and W. T. Ambrosius. 2015. A randomized trial of intensive versus standard blood pressure control. The New England Journal of Medicine 373(22):2103–2116.

Steyerberg, E. W., A. J. Vickers, N. R. Cook, T. Gerds, M. Gonen, N. Obuchowski, M. J. Pencina, and M. W. Kattan. 2010. Assessing the performance of prediction models: A framework for some traditional and novel measures. Epidemiology 21(1):128–138.

Steyerberg, E. W., T. van der Ploeg, and B. Van Calster. 2014. Risk prediction with machine learning and regression methods. Biometrical Journal 56(4):601–606. doi: 10.1002/bimj.201300297.

Sussman, J. B., S. Vijan, H. Choi, and R. A. Hayward. 2011. Individual and population benefits of daily aspirin therapy: A proposal for personalizing national guidelines. Circulation: Cardiovascular Quality and Outcomes 4(3):268–275.

Sussman, J. B., S. Vijan, and R. A. Hayward. 2013. Using benefit-based tailored treatment to improve the use of antihypertensive medications. Circulation 128(21):2309–2317.

Sussman, J. B., D. M. Kent, J. P. Nelson, and R. A. Hayward. 2015. Improving diabetes prevention with benefit based tailored treatment: Risk-based reanalysis of Diabetes Prevention Program. The BMJ 350:h454.

Thune, J. J., D. Hoefsten, M. Lindholm, L. Mortensen, H. Andersen, T. Nielsen, L. Kober, and H. Kelbaek. 2005. Simple risk stratification at admission to identify patients with reduced mortality from primary angioplasty. Circulation 112:2017–2021.

Timbie, J. W., R. A. Hayward, and S. Vijan. 2010. Diminishing efficacy of combination therapy, response-heterogeneity, and treatment intolerance limit the attainability of tight risk factor control in patients with diabetes. Health Services Research 45(2):437–456.

Ting, H. H., J. P. Brito, and V. M. Montori. 2014. Shared decision making: Science and action. Circulation: Cardiovascular Quality and Outcomes 7:323-327. https://doi.org/10.1161/CIRCOUTCOMES.113.000288.

Upshaw, J. N., D. van Klaveren, M. A. Konstam, and D. M. Kent. 2018. Digoxin benefit varies by risk of heart failure hospitalization: Applying the Tufts MC HF risk model. American Journal of Medicine 131(6):676–683.

Vijan, S., T. Hofer, and R. A. Hayward. 1997. Estimated benefits of glycemic control in microvascular complications in type 2 diabetes. Annals of Internal Medicine 127(9):788–795.

Wallentin, L., R. C. Becker, A. Budaj, C. P. Cannon, H. Emanuelsson, C. Held, J. Horrow, S. Husted, S. James, H. Katus, K. W. Mahaffey, B. M. Scirica, A. Skene, P. G. Steg, R. F. Storey, and R. A. Harrington for the PLATO Investigators. 2009. Ticagrelor versus clopidogrel in patients with acute coronary syndromes. The New England Journal of Medicine 361:1045–1057.doi:10.1056/NEJMoa0904327.

Wang, J., M. R. Ban, G. Y. Zou, H. Cao, T. Lin, B. A. Kennedy, S. Anand, S. Yusuf, M. W. Huff, R. L. Pollex, and R. A. Hegele. 2008. Polygenic determinants of severe hypertriglyceridemia. Human Molecular Genetics 17(18):2894–2899.

Wennberg, J., and A. Gittelsohn. 1973. Small area variations in health care delivery. Science 182(4117):1102–1108.

Yang, Q., M. J. Khoury, L. Botto, J. M. Friedman, and W. D. Flanders. 2003. Improving the prediction of complex diseases by testing for multiple disease-susceptibility genes. The American Journal of Human Genetics 72:636–649.

Zimmer, C. 2018. Genetic intelligence tests are next to worthless. The Atlantic, May 29. https://www.theatlantic.com/science/archive/2018/05/genetic-intelligencetests-are-next-to-worthless/561392 (accessed July 2, 2018).