Completed Harm Worksheet for Evidence-Based Geriatric Medicine
Pahor M et al: Calcium-channel blockade and incidence of cancer in aged populations. Lancet 1996;348:493-7. (also see 487-9 and 541-2)
Are the results of this harm study valid?
Were there clearly defined groups of patients, similar in all important ways other than exposure to the treatment or other cause?
Clearly defined, but heterogeneous. Exposed individuals different from non-exposed (more diabetes and cardiovascular disease, disability, hospitalisation, but lower diastolic pressure), but both groups cancer-free at the start of the study.
Were treatment exposures and clinical outcomes measured the same ways in both groups (e.g., was the assessment of outcomes either objective (e.g., death) or blinded to exposure)?
Yes. Asked to show their medications, and clinical outcomes measured the same way in both groups.
Was the follow-up of study patients complete and long enough?
Averaged 3.7 years, and long enough to show a positive relationship between CCBs and cancer. But there were only 47 cancers in 1549 person-years of CCB taking.
Do the results satisfy some "diagnostic tests for causation"?
Is it clear that the exposure preceded the onset of the outcome?
Probably; excluded everyone with known cancer at the start (still may have been some smouldering).
Is there a dose-response gradient?
Yes (figure 2)
Is there positive evidence from a "dechallenge-rechallenge" study?
Is the association consistent from study to study?
Does the association make biological sense?
Whether interference with apoptotic destruction of cancer cells is sensible is hotly debated.
BUT: Was this a previously generated hypothesis, or was it one of several analyses carried out on a large data set of drugs and diseases? (We've written to the authors about this and Dr. Pahor has informed us that this hypotheses was generated prior to the study onset.)
Are the valid results of this randomised trial important?
|Present (Case)||Absent (Control)|
|Exposed to the treatment||Yes (Cohort)||
a + b
c + d
a + c
b + d
In this study:
Relative Risk (RR) = 3.03%/2.17%
Relative Risk (RR)= 1.4 (P = 0.032)
(and when adjusted for several baseline differences, RR ROSE (!) to 1.7 (P = 0.0005)).
Should these valid, potentially important results of a critical appraisal about a harmful treatment change the treatment of your patient?
Can the study results be extrapolated to your patient?
Depends on whether you believe them. If you do believe them, they can be extrapolated to your patient.
What are your patient's risks of the adverse outcome?
To calculate the NNH for any Odds Ratio (OR) and your Patient's Expected Event Rate for this adverse event if they were NOT exposed to this treatment (PEER):
If we assume our patient is like the average individual in this study (the hazard ratios are like odds ratios and don't differ in important ways between subgroups), then his Absolute Risk Increase in cancer over 3.7 years is 3.03% - 2.17% = 0.86% = and 1/0.86% gives an NNH of 116.
What are your patient's preferences, concerns and expectations from this treatment?
Need to be determined.
What alternative treatments are available?
Lots of alternative treatments available for his hypertension (thiazides, beta-blockers). They have their own side-effects but are not reputed to cause cancer.
Other case-control and cohort studies vary in their conclusions about CCB risks, and a meta-analysis is awaited.
Until it is sorted out, you could describe NNHs (and possible NNHs) for alternative antihypertensive regimens with your patient and the two of you could collaborate in deciding on the most appropriate one for him.