Critical appraisal:Cook NR, Lee IM, Gaziano JM, Gordon D, Ridker PM, Manson JE, et al 2005 2

From Cancer Guidelines Wiki
Jutta's tick icon.png This appraisal has been completed.


Article
Cook NR, Lee IM, Gaziano JM, Gordon D, Ridker PM, Manson JE, et al. Low-dose aspirin in the primary prevention of cancer: the Women's Health Study: a randomized controlled trial. JAMA 2005 Jul 6;294(1):47-55 Available from: http://www.ncbi.nlm.nih.gov/pubmed/15998890.
Assigned to
User:Krishna.sriram
Topic area
Guidelines:Lung cancer/Prevention and diagnosis
Clinical question
Form
Form:Critical appraisal
Study design
randomised controlled trial
Level of Evidence
II

Section below only relevant for Cancer Council Project Officer

Edit appraisal assignment


Critical Appraisal

Article being appraised

Cook NR, Lee IM, Gaziano JM, Gordon D, Ridker PM, Manson JE, et al. Low-dose aspirin in the primary prevention of cancer: the Women's Health Study: a randomized controlled trial. JAMA 2005 Jul 6;294(1):47-55 Available from: http://www.ncbi.nlm.nih.gov/pubmed/15998890.


Applicable clinical question

Key Facts

Study Design

randomised controlled trial

Study aims:

To examine the effect of aspirin on the risk of cancer incidence and cancer specific mortality among healthy women.

Number of Patients:

39876

A dose of 100 mg of aspirin (n=19 934) or aspirin placebo (n=19 942) administered every other day.
Reported outcome(s):

Primary outcome: Confirmed newly diagnosed invasive cancer at any site, except for nonmelanoma skin cancer.

Secondary outcomes: Incidence of breast, colorectal, and lung cancer.

Results of outcome(s):

a. No effect of aspirin was observed on total cancer (n=2865; relative risk [RR], 1.01; 95% confidence interval [CI], 0.94-1.08; P=.87), breast cancer (n=1230; RR, 0.98; 95% CI, 0.87-1.09; P=.68), colorectal cancer (n=269; RR,0.97; 95% CI, 0.77-1.24; P=.83).

b. Lung cancer incidence: trend toward reduction in risk (n=205; RR, 0.78; 95% CI, 0.59-1.03; P=.08).

c. No reduction in cancer mortality overall (n=583; RR, 0.95; 95% CI, 0.81-1.11; P=.51).

d. Lung cancer mortality (n=140; RR, 0.70; 95% CI, 0.50-0.99; P=.04).

e. No evidence of differential effects of aspirin by follow-up time or interaction with vitamin E was
found.

Comments on results:

Only 1 other randomized trial of aspirin has examined the impact on cancer incidence. In this study lung cancer deaths were reduced by 36%, an observation that was deemed unanticipated and likely due to data fluctuations.

The Physicians Health Study has unpublished data on lung cancer deaths, which were based on small numbers, were compatible with those found in the WHS and the British trial. In the PHS, there was a nonsignificant 22% reduction in lung cancer mortality in the active aspirin group during the trial period (14 vs 18, P=.48; J. M. Gaziano, written communication, 2005). There was also a 13% reduction in lung cancer incidence (25vs 29, P=.61), with no reduction in total cancer incidence or mortality.

Observational evidence for an effect of aspirin on lung cancer has been mixed.

Thus, although results from the British trial,the PHS, and the WHS are compatible with a reduction in risk of
lung cancer, particularly lung cancer mortality, evidence for such an effect remains uncertain and may simply reflect the play of chance.

Includes an economic evaluation

no

Evidence ratings

Level of evidence

II

Risk of bias
Low risk of bias Comments:

Risk of bias assessment: randomised controlled trial

Was the trial double-blinded?
I am reasonably certain that the trial was double-blinded (eg identical placebo, active placebo, double-dummy, no revealing side-effects).
Was the treatment allocation schedule concealed?
Adequately concealed (e.g. central randomisation, numbered or coded bottles, drugs prepared by pharmacy).
Were all randomised participants included in the analysis?
No exclusions or survival analysis used with all subjects included (>95% follow-up for all groups).
The field below is not considered when calculating the risk of bias rating
How was the allocation schedule generated?
Adequate (e.g. random number table, computer random generator, coin tossing, card shuffling)
Size of effect
2 Reason for decision: Lung cancer incidence and mortality were secondary outcomes.
Result of appraisal

Jutta's tick icon.png Included



Comments

Results of study are probably due to chance rather a real protective effect of aspirin on lung cancer incidence and mortality.

Completed by

Dr Bajee Krishna Sriram, PhD