home   author    contact   web site dedication



Specific guide to this web site for:

 1.  Medical School
      in Statistics

 2.  Medical Students

 3.  Science media writers

 4.  High School & College
     Statistic Teachers


1. Harvard led MI study

2. JACC study 

   (J. of Amer. Coll.

3. NEJM cath study

4. Amer. J. of Cardio.
    review of literature


Oat bran study

Pregnancy & Alcohol

Are Geminis really
9. Columbia 'Miracle' Study  

Additional Topics:


Limitations of Meta-Analyses

Large Randomized Clinical Trials

Tale of Two Large

Advocate meta-analyses

Network meta-analyses




Strengths and potential weaknesses of large randomized clinical trials.

Very large randomized trials can have significant problems in trial construction and interpretation.

The very large randomized clinical trial has many significant advantages.  A major strength is that there are sufficient numbers of patients involved so that the results of the trial are  reproducible if the same trial is repeated in the same patient population.  In addition, a very large trial is usually sufficiently powered for statistically valid prespecified subgroup analyses to be performed. A very large trial greatly increases the probability that repetition of that very same trial would result in the same outcome. 

However, a very large trial does not guarantee that the trial protocol is optimal or that the trial results are broadly applicable or that the conclusions reached are valid. (See Tale of Two Large Trials to examine a superb large trial optimally performed compared to a suboptimally interpreted large trial.)

Does a very large randomized clinical trial guarantee an inherently good trial?

The quality of a very large clinical trial is dependent on having a well constructed treatment protocol to the same degree that a smaller trial is dependent on this issue.  If one or both of the treatment arms of a clinical trial has serious limitations in regards to representing optimal therapy for a particular strategy being evaluated, then the clinical applicability of the results to patient care is less directly meaningful.  (example)  Hence, a very large trial is dependent on the quality of the treatment protocol in regards to the clinical applicability of the trial for physicians managing and treating similar patients.

 Validity of Conclusion of  Large Randomized Clinical Trials

The conclusions that the authors of a very large randomized trial derive from their results are subject to the same potential for author bias as the conclusions that are made in a small study. The authors of both types of studies give an opinion on the strengths and limitations of the study protocol as well as a statement regarding how broadly applicable the trial results are thought to be. The authors can then state conclusions that are a direct reflection of the trial results or make conclusions not truly warranted by their study.

Though there is an admirable tradition of reaching conclusions that conservatively reflect the data in very large clinical trials, this practice of reaching conclusions that are directly derived from the data is not uniformly practiced, even in large randomized trials.