Acceptance of therapeutic innovations into practice requires demonstrating and quantifying a treatment effect, measured as the difference in outcome rates between experimental and control groups of a randomized trial. This mathematical dependency of the treatment effect on the control event rate (ie, the rate of events in the control group) creates a dilemma for medical innovation. Although decreasing control rates signal therapeutic progress, sustained innovation theoretically requires an inexhaustible control rate. For industries dependent on therapeutic innovations, reducing outcome rates becomes both a primary goal and an existential threat.
When sequentially testing treatments with similar relative risk reductions (efficacy, E), the absolute risk reduction (incremental benefit, B) for i th therapeutic trial in the series can be described by the declining exponential function Bi=B1(1−E)i −1. In turn, the required sample size (S) for the i th trial approximates an increasing exponential function, described by the equation Si~S1/(1−E)i −1, and the number of trial participants for each incremental 1% benefit (unit cost, U) increases at twice this rate, described by the equation Ui~U1/(1−E)2(i −1). The rate of change of unit costs, U, is sensitive to the magnitude of the risk reduction, E. The derivation of the formulas used to calculate B, S, and U at the i th generation of treatment trial is available from the author upon request. In this example, the baseline mortality rate is 8% and the relative risk reduction with each therapy is 25% (and B1 is thus 2%).
Some tools below are only available to our subscribers or users with an online account.
Download citation file:
Web of Science® Times Cited: 15
Customize your page view by dragging & repositioning the boxes below.
More Listings atJAMACareerCenter.com >
Enter your username and email address. We'll send you a link to reset your password.
Enter your username and email address. We'll send instructions on how to reset your password to the email address we have on record.
Athens and Shibboleth are access management services that provide single sign-on to protected resources. They replace the multiple user names and passwords necessary to access subscription-based content with a single user name and password that can be entered once per session. It operates independently of a user's location or IP address. If your institution uses Athens or Shibboleth authentication, please contact your site administrator to receive your user name and password.