Portal de Periódicos da CAPES

Learning From Null

2019; Lippincott Williams & Wilkins; Volume: 12; Issue: 12 Linguagem: Inglês

10.1161/circoutcomes.119.006280

1941-7705

James Burke, Brahmajee K. Nallamothu,

Cardiac Health and Mental Health

HomeCirculation: Cardiovascular Quality and OutcomesVol. 12, No. 12Learning From Null Free AccessEditorialPDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessEditorialPDF/EPUBLearning From NullNegative Trials Are Important, Particularly in Low- to Middle-Income Countries James F. Burke, MD and Brahmajee K. Nallamothu, MD, MPH James F. BurkeJames F. Burke James F. Burke, MD, Department of Neurology, University of Michigan, 2800 Plymouth Rd, Bldg 14, Rm G105, Ann Arbor MI 48109. Email E-mail Address: [email protected] Department of Neurology, University of Michigan, Ann Arbor, MI (J.F.B.). and Brahmajee K. NallamothuBrahmajee K. Nallamothu Michigan Integrated Center for Health Analytics and Medical Prediction, Department of Internal Medicine, University of Michigan Medical School, Ann Arbor (B.K.N.). Center for Clinical Management and Research, Ann Arbor VA Medical Center, MI (B.K.N.). Originally published6 Dec 2019https://doi.org/10.1161/CIRCOUTCOMES.119.006280Circulation: Cardiovascular Quality and Outcomes. 2019;12:e006280This article is a commentary on the followingRandomized Trial of an Intervention to Improve Blood Pressure Control in Stroke SurvivorsSee Article by Owolabi et alThe importance of universal trial reporting, regardless of result, is clear. Not only are negative and neutral results essential to understanding the world but they also can inform subsequent trials. To execute a successful and informative randomized controlled trial, innumerable pieces have to fall into place—from design to recruitment to execution to follow-up. Even in situations where resources are optimal, trials commonly fail to inform care because one or more trial elements defy expectations. Executing a trial, then, in a novel environment is an especially daunting prospect—as is the case for the 140/90), systolic BPs decreased in both groups, but without a difference between groups, albeit with very modest statistical power to detect differences. The authors reasonably speculate that the failure of a difference to emerge between groups may be a reflection of the higher intensity care received by the control group, including regular appointment reminders and modest financial incentives for study visits.Every trial has to make difficult value judgments that weigh the potential benefits of collecting additional information against the costs of capturing it. The same logic applies before the trial—is the value of getting high-quality preliminary data worth the time and resources needed to acquire it? Owolabi et al2 judged that it was better to push forward with uncertain assumptions about baseline BP rather than wait to collect the data. It is possible that judgment resulted in a false negative trial. However, in executing the trial, they also collected just the sort of high-quality preliminary data to enable subsequent trials. Assuming that study execution required a moderate number of resources, it is hard to argue with their judgment. Executing trials in trial-naive environments comes with some downside, but if a trial is seen as a pathway to subsequent trials, the magnitude of that downside should not be disqualifying.Moreover, THRIVES is an interesting example of some of the virtues of conducting trials in low- to middle-income countries. First, and most importantly, the need for studies in these novel environments is great and growing over time. Stroke and cardiovascular diseases are emerging as leading causes of death and disability in low- and middle-income countries, and this trend is projected to continue to rapidly increase.3,4 Second, the costs of trial execution are vastly lower. Given the lower costs of labor and inputs, it is entirely plausible that low costs need not imply low quality. Taken together, these 2 points argue that the value of trials in low- to middle-income countries may be considerably greater than in higher income countries. Finally, the different clinical environments in low- to middle resource countries sometimes open up scientific questions that are inaccessible in wealthier countries. If a new technology has already disseminated in a wealthy country, for example, patient and provider expectations may create barriers to randomizing to control/placebo. Conversely, in a predissemination region, these barriers may be less steep.Owolabi et al are to be congratulated for executing a high-quality trial—meeting the enrollment target in a short period of time, maintaining excellent outcome follow-up, and, we suspect, doing so with limited resources—in an environment where prior trial infrastructure was limited and preliminary data was lacking. Although it may be disappointing that the trial was negative, if this work is built upon in subsequent trials, the value of this negative study may easily outpace the value of many positive studies in more richly resourced regions.DisclosuresDr Nallamothu is a principal investigator or coinvestigator on research grants from the National Institutes of Health, Department of Veteran's Affairs, Health Services Research and Development, the American Heart Association, and Apple, Inc. He also receives compensation as Editor-in-Chief of Circulation: Cardiovascular Quality and Outcomes, a journal of the American Heart Association. Finally, he is a coinventor on US Utility Patent Number US15/356,012 (US20170148158A1) entitled "Automated Analysis of Vasculature in Coronary Angiograms" that uses software technology with signal processing and machine learning to automate the reading of coronary angiograms, held by the University of Michigan. The patent is licensed to AngioInsight, Inc, in which Dr Nallamothu holds ownership shares. The other author reports no conflicts.FootnotesThe opinions expressed in this article are not necessarily those of the editors or of the American Heart Association.James F. Burke, MD, Department of Neurology, University of Michigan, 2800 Plymouth Rd, Bldg 14, Rm G105, Ann Arbor MI 48109. Email [email protected]umich.eduReferences1. luo J, Wu M, Chen W. Geographical distribution and trends of clinical trial recruitment sites in developing and developed countries.J Health Inform Dev Ctries. 2017; 11:1–18.Google Scholar2. Owolabi MO, Gebregziabher M, Akinyemi RO, Akinyemi JO, Akpa O, Olaniyan O, Salako BL, Arulogun O, Tagge R, Uvere E, Fakunle A, Ovbiagele B. Randomized trial of an intervention to improve blood pressure control in stroke survivors.Circ Cardiovasc Qual Outcomes. 2019; 12:e005904. doi: 10.1161/CIRCOUTCOMES.119.005904LinkGoogle Scholar3. Gaziano TA, Bitton A, Anand S, Abrahams-Gessel S, Murphy A. Growing epidemic of coronary heart disease in low- and middle-income countries.Curr Probl Cardiol. 2010; 35:72–115. doi: 10.1016/j.cpcardiol.2009.10.002CrossrefMedlineGoogle Scholar4. Nowbar AN, Gitto M, Howard JP, Francis DP, Al-Lamee R. Mortality from ischemic heart disease.Circ Cardiovasc Qual Outcomes. 2019; 12:e005375. doi: 10.1161/CIRCOUTCOMES.118.005375LinkGoogle Scholar Previous Back to top Next FiguresReferencesRelatedDetailsCited ByNallamothu B, Schultz J and Petty S (2020) True Negatives, Circulation: Cardiovascular Quality and Outcomes, 13:10, (e007448), Online publication date: 1-Oct-2020.Related articlesRandomized Trial of an Intervention to Improve Blood Pressure Control in Stroke SurvivorsMayowa O. Owolabi, et al. Circulation: Cardiovascular Quality and Outcomes. 2019;12 December 2019Vol 12, Issue 12 Advertisement Article InformationMetrics © 2019 American Heart Association, Inc.https://doi.org/10.1161/CIRCOUTCOMES.119.006280PMID: 31805786 Originally publishedDecember 6, 2019 Keywordsblood pressureEditorialsstrokeincomerisk factorPDF download Advertisement SubjectsHigh Blood PressureHypertensionSecondary Prevention