What IST going on?

OK. I realise the idea of a medical blog is to spread knowledge and inspire my fellow internet savvy clinicians. However today I am writing about ignorance. Specifically mine. I am deeply confused. No matter how hard I try, I can’t get my head around this, and I’m writing in the hope that someone will enlighten me.   DrGDH

What could be getting be so confused you ask? I’ll tell you.

IST-3

I’d been looking forward to this trial (as much as one can look forward to a piece of research….). It was supposed to make things clear. Is stroke thrombolysis really as good as neurologists keep telling me? Is it really OK in an 85 yr old? Is it really OK to give at 4.5 hrs? A 3000 patient RCT, comparing stroke patients given rT-PA to a control group will answer all my questions.

It was supposed to be great.

Imagine my delight when, on skipping straight to the conclusion I read

“thrombolysis improved functional outcome“

and

“benefit did not seem to be diminished in elderly patients“

Great!

I should have stopped there, I could have gone away happy then, prescribing powerful thrombolytics to all and sundry. But, a nagging sense of responsibility remained, and, against my better judgement, I sat and read the rest of the paper.

I was pleased to see the treatment and control cohorts were well matched; a common complaint about some of the previous stroke thrombolysis literature is that more severe strokes were going in the control groups.

It was on reading through the method I began to have doubts. Non blinded?

The patient selection confused me somewhat as well.

If the admitting doctor really wanted to give the patient thrombolysis, then they did, and the patients was excluded. if they really didn’t want to, then they didn’t get it, and the patient was excluded. The patients in the trial were those for who thrombolysis was “promising but unproven”.

Patients selected for the trial because they were “promising” ?? My resolve was shaken, but OK, they were looking at patients who fell outside the ‘accepted’ indications.

I read on. Surely it would all become clear?

Th outcome measures were reassuring. A nice solid primary outcome: the number of patients alive and independent at 6 months.

The trial finished with 3035 patients. They didn’t reach their goal of 6000 patients, but compared to other stroke thrombolysis trials, this is huge. I was encouraged.

On to the results then. I had read the conclusion already so knew what to expect.

Of 1515 patients who got thrombolysis 554 (36.5%) were independent at 6 months. Of 1520 controls, 534 (35.1%) were independent at 6 months.

This didn’t seem right…. a 1.4% difference doesn’t seem like much at all.

And there it was: p = 0.181.

There was no significant difference in the primary outcome.

A sense of self doubt set in, what was I missing? How do the authors go from that to “thrombolysis improved functional outcome”. A search through the text provides a possible explanation

“A secondary ordinal analysis provided evidence of a favourable shift in the distribution of OHS scores at 6 months with treatment“.

Further self doubt, I don’t know what a ‘secondary ordinal analysis’ is. A nagging thought occurs…. this sounds like statistical voodoo to me….

Having found no answers in the paper itself I took to the Internet. Surely someone in the blogotwittersphereverse as an explanation?!

However, it seems that everyone else is as baffled as I am. Even the great Dr Newman of the NNT.com could not explain it, concluding that the authors have gone “stark raving mad” and their conclusion is “delusional” . Other trusted sources are similarly unimpressed; EM literature of Note and Emergency Medicine Ireland both conclude it is a negative trial.

So no answers there then. How this trial can be considered positive, when it is negative for its primary outcome? Are we to agree with Dr Newmans conclusion and question the sanity of the authors?

I hope not. Surely there must be someone out there who can explain this to a confused ED Doc? Answers on a post card please…. or failing that, comment below.

Until then, I’m going to struggle to factor IST-3 into my ‘informed consent’ spiel…….

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