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Special Communication |

Assessing Differences in Clinical Trials Comparing Surgical vs Nonsurgical Therapy: Title and subTitle BreakUsing Common (Statistical) Sense

George Howard, DrPH; Lloyd E. Chambless, PhD; Richard A. Kronmal, PhD
[+] Author Affiliations

Reprints: George Howard, DrPH, Department of Public Health Sciences, Bowman Gray School of Medicine of Wake Forest University, Winston-Salem, NC.


From the Department of Public Health Sciences, Bowman Gray School of Medicine of Wake Forest University, Winston-Salem, NC (Dr Howard); the Department of Biostatistics, University of North Carolina at Chapel Hill (Dr Chambless); and the Department of Biostatistics, University of Washington, Seattle (Dr Kronmal).


JAMA. 1997;278(17):1432-1436. doi:10.1001/jama.1997.03550170062033
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The statement of hypotheses and choice of statistical tests in clinical trials that compare surgical with nonsurgical treatment are complicated by the likelihood of excess risk in the surgical group during the perioperative period but lower risk after that compared with the more uniform risk in the nonsurgical group. Commonly used statistical survival analyses implicitly assume a constant ratio of risks in the 2 groups during the follow-up period. However, the changing pattern of risk for one treatment but not the other implies that the assessment of the relative efficacy of the treatments varies with the length of the follow-up. As such, determining whether survival curves for the 2 groups are different may not translate easily into selecting the best treatment. Alternative statements of the hypothesis based on consideration of the time horizon of patients and on clinical judgment may be more consistent with the goals of the study. Regardless of the choice of a statistical test, the choice of treatment is a decision specific to the individual patient and should be influenced by the patient's life expectancy, attitude toward taking risks, quality of life, and cost considerations. When the survival curves cross, there is a trade-off between the risk of surgery and the increase in life expectancy among the survivors of surgery. Accordingly, assessment of differences in outcomes in clinical trials comparing surgical vs nonsurgical therapy should provide both a conclusion about whether 1 treatment can reasonably be considered best for most patients and should provide information to the individual patient and physician on the expected outcome to aid in the decision-making process.

REFERENCES

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The Asymptomatic Carotid Atherosclerosis Study Group.  Study design for randomized prospective trial of carotid endarterectomy for asymptomatic atherosclerosis . Stroke . 1989;;20:844-849.
Executive Committee for the Asymptomatic Carotid Atherosclerosis Study.  Endarterectomy for asymptomatic carotid artery stenosis . JAMA . 1995;; 273:1421-1428.
Principal Investigators of CASS and Their Associates.  The National Heart, Lung, and Blood Institute Coronary Artery Surgery Study . Circulation . 1981;;63:( (suppl 1) ):I1-I81.
CASS Principal Investigators and Their Associates.  Myocardial infarction in the Coronary Artery Surgery Study (CASS) randomized trial . N Engl J Med . 1984;;310:750-758.
Friedman LM, Furberg CD, DeMets DL. Fundamentals of Clinical Trials . St Louis, Mo: MosbyYear Book Inc; 1996;.
Sacks FM, Pfeffer MA, Moye LE, et al.  The effect of pravastatin on coronary events after myocardial infarction in patients with average cholesterol levels . N Engl J Med . 1996;;335:1001-1009.
Fisher CJ, Slotman GJ, Opal SM, et al.  The IL1RA Sepis Syndrome Study Group, initial evaluation of human recombinant interleukin 1 receptor antagonist in the treatment of sepsis syndrome . Crit Care Med . 1994;;22:12-21.
O'Brien PC, Fleming TR.  A multiple testing procedure for clinical trials . Biometrics . 1979;;35:549-556.
Lan KKG, DeMets DL.  Discrete sequential boundaries for clinical trials . Biometrika . 1983;;70:659-663.
Miller RG Jr. Simultaneous Statistical Inference . 2nd ed. New York, NY: Springer-Verlag NY Inc; 1981;.

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Bonadonna G, Zambetti M, Valagussa P.  Sequential or alternating doxorubicin and CMF regimens in breast cancer with more than three positive nodes: ten-year results . JAMA . 1995;;273:542-547.
Elandt-Johnson RC, Johnson NL. Survival Models and Data Analysis . New York, NY: John Wiley & Sons Inc; 1980;.
Kalbfleisch JD, Prentice RL. The Statistical Analysis of Failure Time Data . New York, NY: John Wiley & Sons Inc; 1980;.
Flemming TR, Harrington DP. Counting Processes and Survival Analysis . New York, NY: John Wiley & Sons Inc; 1991;.
Gill RD, Schumacher M.  A simple test of the proportional hazards assumption . Biometrika . 1987;;74:289-300.
Lee ET, Desu MM, Gehan EA.  A Monte-Carlo study of the power of some two-sample tests . Biometrika . 1975;;62:425-432.
The Asymptomatic Carotid Atherosclerosis Study Group.  Study design for randomized prospective trial of carotid endarterectomy for asymptomatic atherosclerosis . Stroke . 1989;;20:844-849.
Executive Committee for the Asymptomatic Carotid Atherosclerosis Study.  Endarterectomy for asymptomatic carotid artery stenosis . JAMA . 1995;; 273:1421-1428.
Principal Investigators of CASS and Their Associates.  The National Heart, Lung, and Blood Institute Coronary Artery Surgery Study . Circulation . 1981;;63:( (suppl 1) ):I1-I81.
CASS Principal Investigators and Their Associates.  Myocardial infarction in the Coronary Artery Surgery Study (CASS) randomized trial . N Engl J Med . 1984;;310:750-758.
Friedman LM, Furberg CD, DeMets DL. Fundamentals of Clinical Trials . St Louis, Mo: MosbyYear Book Inc; 1996;.
Sacks FM, Pfeffer MA, Moye LE, et al.  The effect of pravastatin on coronary events after myocardial infarction in patients with average cholesterol levels . N Engl J Med . 1996;;335:1001-1009.
Fisher CJ, Slotman GJ, Opal SM, et al.  The IL1RA Sepis Syndrome Study Group, initial evaluation of human recombinant interleukin 1 receptor antagonist in the treatment of sepsis syndrome . Crit Care Med . 1994;;22:12-21.
O'Brien PC, Fleming TR.  A multiple testing procedure for clinical trials . Biometrics . 1979;;35:549-556.
Lan KKG, DeMets DL.  Discrete sequential boundaries for clinical trials . Biometrika . 1983;;70:659-663.
Miller RG Jr. Simultaneous Statistical Inference . 2nd ed. New York, NY: Springer-Verlag NY Inc; 1981;.
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