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Specific guide to this web site for:

 1.  Medical School
      Educators 
      in Statistics

 2.  Medical Students

 3.  Science media writers

 4.  High School & College
     Statistic Teachers

   Misadventures:

1. Harvard led MI study

2. JACC study 
   (J. of Amer. Coll.
   Cardio.)

3. NEJM cath study

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

5. ALLHAT
    controversy 

6. Oat bran study

7. Pregnancy & Alcohol

8. Are Geminis really
    different?
      
9. Columbia 'Miracle' Study  
                                                 

Additional Topics:

Celebrex

Limitations of Meta-Analyses

Large Randomized Clinical Trials

Tale of Two Large
Trials

Advocate meta-analyses

Network meta-analyses

   Unreliable ALLHAT Correction Estimations for Differences in Blood Pressures

The ALLHAT authors substantially underestimate the effect on outcome of the 3mm difference in systolic blood pressure that occurred between diuretic arm compared to ACE inhibitor arm.

Blood pressure studies comparing a combination of medications should ideally create treatment protocols where the medications are adjusted until the same blood pressure is achieved in each treatment arm of the trial, if possible.  The 3 mm lower systolic blood pressure that was present with the diuretic treatment protocol strongly favored the diuretic initiated therapy.

The statistical manipulations and estimations used to correct for the differences in trial outcome resulting from this difference in blood pressure in the ALLHAT study are inaccurate. 

The ALLHAT authors attempt to statistically correct for the difference in blood pressure between the groups and appear to have substantially underestimated the effects of creating blood treatment protocols that did not obtain the same levels of blood pressure control in their study.

The underestimation of the effect of the difference in systolic blood pressure on outcome is demonstrated in the ALLHAT authors' discussion of stroke rate in the black patients in the trial:

 The ALLHAT investigators while discussing differences in stroke rate in black patients between diuretic and ACE inhibitor protocols in their initial 2002 report state that the 4mm difference in systolic blood pressure is not consistent  "with the difference seen in black patients (13%-16% expected, 40% increase in stroke rate observed)." Hence, the ALLHAT investigators are saying that the 4mm difference in systolic blood pressure for black patients for diuretic led therapy vs. ACE inhibitor led therapy explains only a 13-16% difference in stroke rate, not the 40% difference in stroke rate observed.  
(The black patient population was the subgroup in the ALLHAT trial which had the largest difference in blood pressure (4mm) between the diuretic initiated treatment protocol vs. the lisinopril protocol and accounted for all the increased incidence in stroke in the initial ALLHAT 2002 report.)

There is no reason to accept the implication by the ALLHAT investigators that it is more reasonable to assume there are special protective properties in the diuretic beyond the well established efficacy of a diuretic on BP control in the black population. 

The ALLHAT's attempts to quantify the effects of the differences in blood pressure between the 3 blood pressure treatment protocols on the trial outcome are unreliable.  To quote the ALLHAT investigators:
    "However, such analyses are limited by the infrequency and imprecision of BP measurements for individual participants and regression dilution, which underestimates CVD risk associated with BP differences on single-visit (or even visit-averaged) measurements."¹

The estimation by the ALLHAT authors on the impact of the blood pressure differences on patient outcome for the different blood pressure regimens is inaccurate.

1. ALLHAT Officers and Coordinators for the ALLHAT Collaborative Research Group. Major outcomes in high-risk hypertensive patients randomized to angiotensin-converting enzyme inhibitor or calcium channel blocker vs. diuretic: the antihypertensive and lipid-lowering treatment to prevent heart attack trial (ALLHAT). JAMA 2002; 288: p 2991

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