Dr. Eric Lim's Weblog

So, once again, Aprotinin is bad.

In the New England Journal of Medicine, the Perioperative Ischaemia Research Group just published the results of a large observational study encouraging readers not to use aprotinin after cardiac surgery. One of the main reasons cited in the paper was a doubling in the risk of renal dysfunction and renal failure.

The study is to be commended on the large sample size, an impressive 4374 patients in 69 institutions across the world. Whilst we, as readers and reviewers are often wary about conclusions based on small sample sizes concluding no difference when a true difference might exist, why don’t we display a similar scepticism about large studies that conclude a difference when none might exist?

Big is not always better, the authors state that in this setting, a randomised trial would be ideal but would be difficult “if not impossible” to conduct, and observational studies when sufficiently large may offer critical insights even in light of recognized limitations.

Unfortunately they are missing the point. A small randomised trial will give you an estimate that is closer to the truth, because baseline differences are balanced, but the results may be imprecise (wide confidence interval) that is progressively narrowed by increasing the sample size.

However, a large observational study may give you a very precise estimate, but it may be far from the truth (influenced by bias arising from differences in the groups compared), that can never be corrected by increasing the sample size.

Precision of the estimate is never more important than a correct estimate!

Continue reading "Aprotinin: propensity for confusion" »

Posted by Eric Lim at 08:28 AM | Permalink

There is a great article by Professor David Taggart , also mentioned by Professor Tom Treasure, about the current interpretation of clinical trials comparing PCI (mainly stenting) against CABG. One of the main premises is that cardiologists are not providing the standard of care of revascularization, stemming from (or is justified by) revascularization trials that include a significant proportion of patients with coronary disease distribution that are known not to derive survival benefit with CABG.

Whilst I would love nothing more than to support any cause that would lead to more work for the specialty, I think there is more to the debate.

Wouldn’t it be really unethical to randomize patients with coronary disease anatomy that are already known to derive a survival benefit from CABG to receive PCI? Also, there is no onus to prove that CABG is superior. As far as I can see, the PCI trials ask a different question: `in patients who are amenable to both form of treatment, is there any difference in the outcome between PCI and CABG?’. The trials mainly have the same message, which is lower re-intervention with CABG and no difference in survival. An interesting exception is the SOS trial, where survival was statistically significantly improved with CABG, but the result was glossed over by the reporting authors ("The apparent reduction in mortality with CABG requires further investigation").

We will never stand a fair chance in any revascularization war.

Continue reading "Revascularization wars" »

Posted by Eric Lim at 05:09 PM | Permalink

I love being in an era where new technology is being evaluated. I sat in a lecture by a famous liver surgeon (Alan Johnson) in Sheffield (UK, where they filmed the `Full Monty’) prior to his retirement. He said that he had seen it all with regards to surgical research. It always follows the same pattern. First everyone loves a new surgical advancement, then everyone hates it, then we find indications for its appropriate use.

I think off-pump surgery is between phase 1 and 2 of the `Johnson chronology’. What really amuses me is how evangelical surgeons can be when defending their preferred technique. The sentiments are best reflected in this great quote:

`To cut things short, it is extremely important to understand that there is abundant clinically relevant though not necessarily statistically significant, scientific evidence to validate the midterm safety and efficacy of OPCAB.’ Anesthesiology 2005; 103: 902.

Frankly, surgical research can never be 100% replicable and reporting can never be 100% free from bias. The variances in patient response to a tablet (due to pharmacokinetics, pharmacodynamics differences) are usually balanced out if a trial is large enough, but no two surgeons will operate with the same skill. A new procedure that is shown to be superior compared to the standard in the hands of gifted surgeon A, may be inferior to the standard in two-left-hands surgeon B.

Continue reading "Off-pump or off handed?" »

Posted by Eric Lim at 02:42 PM | Permalink