my 2 cents: 

Bradford-Hill is one reference list I always refer too even if via a RCT. yet Hill cautioned 

"None of my nine viewpoints can bring indisputable evidence for or against the cause-and-effect hypothesis and none can be required sine qua non". 

This point is key and maybe one can argue that it seems based on the evidence (if you feel strongly enough that your results point to causation) that 'a causal association seems to exist, based on a balance of probability'.....I dont think one can say 100%....we are always operating in the realm of probability in this area...

  1. Strength: A small association does not mean that there is not a causal effect, though the larger the association, the more likely that it is causal.
  2. Consistency: Consistent findings observed by different persons in different places with different samples strengthens the likelihood of an effect.
  3. Specificity: Causation is likely if a very specific population at a specific site and disease with no other likely explanation. The more specific an association between a factor and an effect is, the bigger the probability of a causal relationship.[12]
  4. Temporality: The effect has to occur after the cause (and if there is an expected delay between the cause and expected effect, then the effect must occur after that delay).
  5. Biological gradient: Greater exposure should generally lead to greater incidence of the effect. However, in some cases, the mere presence of the factor can trigger the effect. In other cases, an inverse proportion is observed: greater exposure leads to lower incidence.
  6. Plausibility: A plausible mechanism between cause and effect is helpful (but Hill noted that knowledge of the mechanism is limited by current knowledge).
  7. Coherence: Coherence between epidemiological and laboratory findings increases the likelihood of an effect. However, Hill noted that "... lack of such [laboratory] evidence cannot nullify the epidemiological effect on associations".
  8. Experiment: "Occasionally it is possible to appeal to experimental evidence".
  9. Analogy: The effect of similar factors may be considered.


Paul E. Alexander

From: "Djulbegovic, Benjamin" <[log in to unmask]>
To: [log in to unmask]
Sent: Fri, January 28, 2011 10:06:33 AM
Subject: Can RCT help establish causation?

Dear all
I'd like to post this question to the group that I have been thinking about for some time... Is there a scientific method that allows us to LOGICALLY  distinguish the cause-effect from the coincidence? David Hume, one of the most influential philosophers of all times, concluded that there is no such a  method. This was before RCTs were "invented". Many people have made cogent arguments that (a well done) RCT is the ONLY method that can allow us to draw the inferences about causation. Because this is not possible in the observational studies, RCTs are considered (all other things being equal) to provide more credible evidence than non-RCTs. However, some philosophers have challenged this supposedly unique feature of RCT- they claim that RCTs  cannot (on theoretical and logical ground) establish the relationship between the cause and effect any better than non-RCTs. I would appreciate some thoughts from the group:
1. Can RCT distinguish between the cause and effect vs. coincidences? (under which -theoretical- conditions?) 
If the answer is "no", is there any other method that can help establish the cause and effect relationship?
I believe the answer to this question is of profound relevance to EBM.

 Ben Djulbegovic