{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,14]],"date-time":"2026-02-14T05:48:34Z","timestamp":1771048114780,"version":"3.50.1"},"reference-count":41,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2019,8,21]],"date-time":"2019-08-21T00:00:00Z","timestamp":1566345600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2019,8,21]],"date-time":"2019-08-21T00:00:00Z","timestamp":1566345600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["npj Digit. Med."],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Currently, clinicians rely mostly on population-level treatment effects from RCTs, usually considering the treatment's benefits. This study proposes a process, focused on practical usability, for translating RCT data into personalized treatment recommendations that weighs benefits against harms and integrates subjective perceptions of relative severity. Intensive blood pressure treatment (IBPT) was selected as the test case to demonstrate the suggested process, which was divided into three phases: (1) Prediction models were developed using the Systolic Blood-Pressure Intervention Trial (SPRINT) data for benefits and adverse events of IBPT. The models were externally validated using retrospective Clalit Health Services (CHS) data; (2) Predicted risk reductions and increases from these models were used to create a yes\/no IBPT recommendation by calculating a severity-weighted benefit-to-harm ratio; (3) Analysis outputs were summarized in a decision support tool. Based on the individual benefit-to-harm ratios, 62 and 84% of the SPRINT and CHS populations, respectively, would theoretically be recommended IBPT. The original SPRINT trial results of significant decrease in cardiovascular outcomes following IBPT persisted only in the group that received a \u201cyes-treatment\u201d recommendation by the suggested process, while the rate of serious adverse events was slightly higher in the \"no-treatment\" recommendation group. This process can be used to translate RCT data into individualized recommendations by identifying patients for whom the treatment\u2019s benefits outweigh the harms, while considering subjective views of perceived severity of the different outcomes. The proposed approach emphasizes clinical practicality by mimicking physicians\u2019 clinical decision-making process and integrating all recommendation outputs into a usable decision support tool.<\/jats:p>","DOI":"10.1038\/s41746-019-0156-3","type":"journal-article","created":{"date-parts":[[2019,8,21]],"date-time":"2019-08-21T10:03:05Z","timestamp":1566381785000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Translating clinical trial results into personalized recommendations by considering multiple outcomes and subjective views"],"prefix":"10.1038","volume":"2","author":[{"given":"Noa","family":"Dagan","sequence":"first","affiliation":[]},{"given":"Chandra J.","family":"Cohen-Stavi","sequence":"additional","affiliation":[]},{"given":"Meytal","family":"Avgil Tsadok","sequence":"additional","affiliation":[]},{"given":"Morton","family":"Leibowitz","sequence":"additional","affiliation":[]},{"given":"Moshe","family":"Hoshen","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2650-6192","authenticated-orcid":false,"given":"Tomas","family":"Karpati","sequence":"additional","affiliation":[]},{"given":"Amichay","family":"Akriv","sequence":"additional","affiliation":[]},{"given":"Ilan","family":"Gofer","sequence":"additional","affiliation":[]},{"given":"Harel","family":"Gilutz","sequence":"additional","affiliation":[]},{"given":"Eduardo","family":"Podjarny","sequence":"additional","affiliation":[]},{"given":"Eitan","family":"Bachmat","sequence":"additional","affiliation":[]},{"given":"Ran D.","family":"Balicer","sequence":"additional","affiliation":[]}],"member":"297","published-online":{"date-parts":[[2019,8,21]]},"reference":[{"key":"156_CR1","doi-asserted-by":"publisher","first-page":"407","DOI":"10.1016\/j.pec.2008.07.054","volume":"73","author":"A Barratt","year":"2008","unstructured":"Barratt, A. Evidence Based Medicine and Shared Decision Making: the challenge of getting both evidence and preferences into health care. Patient Educ. Coun. s. 73, 407\u2013412 (2008).","journal-title":"Patient Educ. Coun. s."},{"key":"156_CR2","doi-asserted-by":"publisher","first-page":"i2452","DOI":"10.1136\/bmj.i2452","volume":"353","author":"M McCartney","year":"2016","unstructured":"McCartney, M., Treadwell, J., Maskrey, N. & Lehman, R. Making evidence based medicine work for individual patients. BMJ 353, i2452 (2016).","journal-title":"BMJ"},{"key":"156_CR3","doi-asserted-by":"publisher","DOI":"10.1186\/1745-6215-11-85","volume":"11","author":"DM Kent","year":"2010","unstructured":"Kent, D. M., Rothwell, P. M., Ioannidis, J. P., Altman, D. G. & Hayward, R. A. Assessing and reporting heterogeneity in treatment effects in clinical trials: a proposal. Trials 11, 85 (2010).","journal-title":"Trials"},{"key":"156_CR4","doi-asserted-by":"publisher","first-page":"837","DOI":"10.1093\/eurheartj\/ehu004","volume":"35","author":"J van der Leeuw","year":"2014","unstructured":"van der Leeuw, J., Ridker, P. M., van der Graaf, Y. & Visseren, F. L. Personalized cardiovascular disease prevention by applying individualized prediction of treatment effects. Eur. Heart J. 35, 837\u2013843 (2014).","journal-title":"Eur. Heart J."},{"key":"156_CR5","doi-asserted-by":"publisher","first-page":"176","DOI":"10.1016\/S0140-6736(05)17709-5","volume":"365","author":"PM Rothwell","year":"2005","unstructured":"Rothwell, P. M. Treating individuals 2. Subgroup analysis in randomised controlled trials: importance, indications, and interpretation. Lancet 365, 176\u2013186 (2005).","journal-title":"Lancet"},{"key":"156_CR6","doi-asserted-by":"publisher","first-page":"2485","DOI":"10.1161\/CIRCULATIONAHA.112.000712","volume":"127","author":"JA Dorresteijn","year":"2013","unstructured":"Dorresteijn, J. A. et al. High-dose statin therapy in patients with stable coronary artery disease: treating the right patients based on individualized prediction of treatment effect. Circulation 127, 2485\u20132493 (2013).","journal-title":"Circulation"},{"key":"156_CR7","doi-asserted-by":"publisher","first-page":"1097","DOI":"10.1161\/CIRCULATIONAHA.116.024247","volume":"135","author":"RW Yeh","year":"2017","unstructured":"Yeh, R. W. & Kramer, D. B. Decision tools to improve personalized care in cardiovascular disease: moving the art of medicine toward science. Circulation 135, 1097\u20131100 (2017).","journal-title":"Circulation"},{"key":"156_CR8","doi-asserted-by":"crossref","first-page":"A11","DOI":"10.7326\/ACPJC-2002-136-2-A11","volume":"136","author":"RB Haynes","year":"2002","unstructured":"Haynes, R. B., Devereaux, P. J. & Guyatt, G. H. Clinical expertise in the era of evidence-based medicine and patient choice. ACP J. Club. 136, A11\u2013A14 (2002).","journal-title":"ACP J. Club."},{"key":"156_CR9","doi-asserted-by":"publisher","first-page":"204","DOI":"10.1016\/j.eururo.2012.04.024","volume":"62","author":"A Vickers","year":"2012","unstructured":"Vickers, A. et al. Individualised estimation of the benefit of radical prostatectomy from the Scandinavian Prostate Cancer Group randomized trial. Eur. Urol. 62, 204\u2013209 (2012).","journal-title":"Eur. Urol."},{"key":"156_CR10","doi-asserted-by":"crossref","first-page":"436","DOI":"10.1097\/MOL.0000000000000554","volume":"29","author":"NEM Jaspers","year":"2018","unstructured":"Jaspers, N. E. M., Ridker, P. M., Dorresteijn, J. A. N. & Visseren, F. L. J. The prediction of therapy-benefit for individual cardiovascular disease prevention: rationale, implications, and implementation. Curr. Opin. Lipidol. 29, 436\u2013444 (2018).","journal-title":"Curr. Opin. Lipidol."},{"key":"156_CR11","doi-asserted-by":"publisher","first-page":"1574","DOI":"10.1161\/CIRCULATIONAHA.115.018383","volume":"133","author":"G Thanassoulis","year":"2016","unstructured":"Thanassoulis, G. et al. Individualised statin benefit for determining statin eligibility in the primary prevention of cardiovascular disease. Circulation 133, 1574\u20131581 (2016).","journal-title":"Circulation"},{"key":"156_CR12","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pmed.1002410","volume":"14","author":"S Basu","year":"2017","unstructured":"Basu, S. et al. Benefit and harm of intensive blood pressure treatment: Derivation and validation of risk models using data from the SPRINT and ACCORD trials. PLoS Med. 14, e1002410 (2017).","journal-title":"PLoS Med."},{"key":"156_CR13","doi-asserted-by":"publisher","first-page":"297","DOI":"10.7326\/0003-4819-151-5-200909010-00003","volume":"151","author":"DE Singer","year":"2009","unstructured":"Singer, D. E. et al. The net clinical benefit of warfarin anticoagulation in atrial fibrillation. Ann. Intern Med. 151, 297\u2013305 (2009).","journal-title":"Ann. Intern Med."},{"key":"156_CR14","doi-asserted-by":"publisher","first-page":"1735","DOI":"10.1001\/jama.2016.3775","volume":"315","author":"RW Yeh","year":"2016","unstructured":"Yeh, R. W. et al. Development and validation of a prediction rule for benefit and harm of dual antiplatelet therapy beyond 1 year after percutaneous coronary intervention. JAMA 315, 1735\u20131749 (2016).","journal-title":"JAMA"},{"key":"156_CR15","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.e6572","volume":"345","author":"AG Mulley","year":"2012","unstructured":"Mulley, A. G., Trimble, C. & Elwyn, G. Stop the silent misdiagnosis: patients\u2019 preferences matter. BMJ 345, e6572 (2012).","journal-title":"BMJ"},{"key":"156_CR16","doi-asserted-by":"publisher","first-page":"109","DOI":"10.1186\/1748-5908-6-109","volume":"6","author":"DM Mann","year":"2011","unstructured":"Mann, D. M. et al. Rationale, design, and implementation protocol of an electronic health record integrated clinical prediction rule (iCPR) randomized trial in primary care. Implement Sci. 6, 109 (2011).","journal-title":"Implement Sci."},{"key":"156_CR17","doi-asserted-by":"publisher","DOI":"10.2196\/medinform.4553","volume":"4","author":"T McGinn","year":"2016","unstructured":"McGinn, T. Putting meaning into meaningful use: a roadmap to successful integration of evidence at the point of care. JMIR Med Inform. 4, e16 (2016).","journal-title":"JMIR Med Inform."},{"key":"156_CR18","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.e3996","volume":"344","author":"H Ahmed","year":"2012","unstructured":"Ahmed, H., Naik, G., Willoughby, H. & Edwards, A. G. Communicating risk. BMJ 344, e3996 (2012).","journal-title":"BMJ"},{"issue":"Suppl 1","key":"156_CR19","first-page":"i28","volume":"18","author":"JE Richardson","year":"2011","unstructured":"Richardson, J. E. & Ash, J. S. A clinical decision support needs assessment of community-based physicians. JAMIA 18(Suppl 1), i28\u2013i35 (2011).","journal-title":"JAMIA"},{"key":"156_CR20","doi-asserted-by":"publisher","first-page":"1056","DOI":"10.1111\/jep.12283","volume":"20","author":"CM Martin","year":"2014","unstructured":"Martin, C. M. & Felix-Bortolotti, M. Person-centred health care: a critical assessment of current and emerging research approaches. J. Eval. Clin. Pract. 20, 1056\u20131064 (2014).","journal-title":"J. Eval. Clin. Pract."},{"key":"156_CR21","doi-asserted-by":"publisher","first-page":"194","DOI":"10.1016\/j.ijcard.2014.12.046","volume":"182","author":"J van der Leeuw","year":"2015","unstructured":"van der Leeuw, J. et al. Prediction of absolute risk reduction of cardiovascular events with perindopril for individual patients with stable coronary artery disease - results from EUROPA. Int J. Cardiol. 182, 194\u2013199 (2015).","journal-title":"Int J. Cardiol."},{"issue":"Suppl 2","key":"156_CR22","doi-asserted-by":"publisher","first-page":"ii1","DOI":"10.1136\/heartjnl-2014-305693","volume":"100","author":"JBS3 Board.","year":"2014","unstructured":"JBS3 Board. Joint British Societies' consensus recommendations for the prevention of cardiovascular disease (JBS3). Heart 100(Suppl 2), ii1\u2013ii67 (2014).","journal-title":"Heart"},{"key":"156_CR23","unstructured":"JBS 3: Joint British Societies for the prevention of cardiovascular disease BCS. British Cardiovascular Society. (British Heart Foundation: London, 2019). http:\/\/www.jbs3risk.com. Accessed 3 June 2019."},{"key":"156_CR24","unstructured":"American College of Cardiology. 2019. ASCVDRisk Estimator Plus. http:\/\/tools.acc.org\/ASCVD-Risk-Estimator-Plus. Accessed 3 June 2019."},{"key":"156_CR25","doi-asserted-by":"publisher","first-page":"i6","DOI":"10.1136\/bmj.i6","volume":"352","author":"AJ Vickers","year":"2016","unstructured":"Vickers, A. J., Van Calster, B. & Steyerberg, E. W. Net benefit approaches to the evaluation of prediction models, molecular markers, and diagnostic tests. BMJ 352, i6 (2016).","journal-title":"BMJ"},{"key":"156_CR26","doi-asserted-by":"publisher","first-page":"b605","DOI":"10.1136\/bmj.b605","volume":"338","author":"DG Altman","year":"2009","unstructured":"Altman, D. G., Vergouwe, Y., Royston, P. & Moons, K. G. Prognosis and prognostic research: validating a prognostic model. BMJ 338, b605 (2009).","journal-title":"BMJ"},{"key":"156_CR27","doi-asserted-by":"publisher","first-page":"1733","DOI":"10.1185\/03007995.2014.921611","volume":"30","author":"Z Yuan","year":"2014","unstructured":"Yuan, Z. et al. Relative importance of benefits and risks associated with antithrombotic therapies for acute coronary syndrome: patient and physician perspectives. Curr. Med Res Opin. 30, 1733\u20131741 (2014).","journal-title":"Curr. Med Res Opin."},{"key":"156_CR28","doi-asserted-by":"publisher","first-page":"1578","DOI":"10.1136\/heartjnl-2017-311244","volume":"103","author":"L Albarqouni","year":"2017","unstructured":"Albarqouni, L., Doust, J. & Glasziou, P. Patient preferences for cardiovascular preventive medication: a systematic review. Heart 103, 1578\u20131586 (2017).","journal-title":"Heart"},{"key":"156_CR29","volume-title":"Causal Inference.","author":"MA Hern\u00e1n","year":"2018","unstructured":"Hern\u00e1n, M. A. & Robins, J. M. Causal Inference. (Chapman & Hall\/CRC, forthcoming, Boca Raton, 2018)."},{"key":"156_CR30","unstructured":"The SPRINT Data Analysis Challenge. 2017. https:\/\/challenge.nejm.org\/pages\/home. Accessed 10 May 2017."},{"key":"156_CR31","doi-asserted-by":"publisher","first-page":"2103","DOI":"10.1056\/NEJMoa1511939","volume":"373","author":"JT Wright Jr.","year":"2015","unstructured":"The SPRINT Research Group, Wright, J. T. Jr. et al. A Randomized Trial of Intensive versus Standard Blood-Pressure Control. N. Engl. J. Med. 373, 2103\u20132116 (2015).","journal-title":"N. Engl. J. Med."},{"key":"156_CR32","doi-asserted-by":"publisher","first-page":"532","DOI":"10.1177\/1740774514537404","volume":"11","author":"WT Ambrosius","year":"2014","unstructured":"Ambrosius, W. T. et al. The design and rationale of a multicenter clinical trial comparing two strategies for control of systolic blood pressure: the Systolic Blood Pressure Intervention Trial (SPRINT). Clin. Trials 11, 532\u2013546 (2014).","journal-title":"Clin. Trials"},{"key":"156_CR33","first-page":"22","volume":"2","author":"S Van Buuren","year":"2014","unstructured":"Van Buuren, S. & Groothuis-Oudshoorn, K. MICE: multivariate imputation by chained equations. R. package version 2, 22 (2014).","journal-title":"R. package version"},{"key":"156_CR34","doi-asserted-by":"publisher","first-page":"681","DOI":"10.1002\/(SICI)1097-0258(19990330)18:6<681::AID-SIM71>3.0.CO;2-R","volume":"18","author":"S Van Buuren","year":"1999","unstructured":"Van Buuren, S., Boshuizen, H. C. & Knook, D. L. Multiple imputation of missing blood pressure covariates in survival analysis. Stat. Med. 18, 681\u2013694 (1999).","journal-title":"Stat. Med."},{"key":"156_CR35","doi-asserted-by":"publisher","first-page":"39","DOI":"10.1002\/sim.4780040107","volume":"4","author":"CH Chen","year":"1985","unstructured":"Chen, C. H. & George, S. L. The bootstrap and identification of prognostic factors via Cox's proportional hazards regression model. Stat. Med. 4, 39\u201346 (1985).","journal-title":"Stat. Med."},{"key":"156_CR36","unstructured":"Steyerberg E. W. Clinical Prediction Models: A Practical Approach to Development, Validation, and Updating. 1st ed. (Springer, 2009)."},{"key":"156_CR37","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2288-9-57","volume":"9","author":"A Marshall","year":"2009","unstructured":"Marshall, A., Altman, D. G., Holder, R. L. & Royston, P. Combining estimates of interest in prognostic modelling studies after multiple imputation: current practice and guidelines. BMC Med. Res. Methodol. 9, 57 (2009).","journal-title":"BMC Med. Res. Methodol."},{"key":"156_CR38","doi-asserted-by":"publisher","first-page":"601","DOI":"10.1161\/CIRCULATIONAHA.115.017719","volume":"133","author":"PC Austin","year":"2016","unstructured":"Austin, P. C., Lee, D. S. & Fine, J. P. Introduction to the analysis of survival data in the presence of competing risks. Circulation 133, 601\u2013609 (2016).","journal-title":"Circulation"},{"key":"156_CR39","doi-asserted-by":"publisher","first-page":"496","DOI":"10.1080\/01621459.1999.10474144","volume":"94","author":"JP Fine","year":"1999","unstructured":"Fine, J. P. & Gray, R. J. A proportional hazards model for the subdistribution of a competing risk. J. Am. Stat. Assoc. 94, 496\u2013509 (1999).","journal-title":"J. Am. Stat. Assoc."},{"key":"156_CR40","unstructured":"Efron, B. & Tibshirani, R. J. Cross-validation and the bootstrap: estimating the error rate of a prediction rule. (Division of Biostatistics, Stanford University, 1995)."},{"key":"156_CR41","doi-asserted-by":"publisher","first-page":"515","DOI":"10.7326\/0003-4819-130-6-199903160-00016","volume":"130","author":"AC Justice","year":"1999","unstructured":"Justice, A. C., Covinsky, K. E. & Berlin, J. A. Assessing the generalizability of prognostic information. Ann. Intern Med. 130, 515\u2013524 (1999).","journal-title":"Ann. Intern Med."}],"container-title":["npj Digital Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41746-019-0156-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41746-019-0156-3","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41746-019-0156-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,12,17]],"date-time":"2022-12-17T18:31:54Z","timestamp":1671301914000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41746-019-0156-3"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,8,21]]},"references-count":41,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2019,12]]}},"alternative-id":["156"],"URL":"https:\/\/doi.org\/10.1038\/s41746-019-0156-3","relation":{},"ISSN":["2398-6352"],"issn-type":[{"value":"2398-6352","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,8,21]]},"assertion":[{"value":"6 December 2018","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"3 July 2019","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"21 August 2019","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"81"}}