Ann: Mesoblast Phase 3 CLBP Trial Completes Enrollment, page-145

Probably speculative markets do operate to make the rich richer. This might be a good thing … as those richer people are probably cleverer and will put the money to better use.

But what is fascinating (at least to me) is how our market system influences clinical trials.

Take this innocuous statement from MSB:

“The 2:1 randomized, placebo-controlled Phase 3 trial (NCT02412735) enrolled 404 patients across 48 centers in the United States and Australia. Following completion of the planned enrollment of 360 patients, all additional patients still in screening at that point were allowed to complete enrollment.”

The 2:1 randomisation allocation means a participant has 2 chances in 3 of receiving the intervention compared to 1 chance in 3 of receiving the placebo. Good odds for the participant but a less efficient design than 1:1 allocation.

If it is less efficient why is it done? To make the study easier to recruit to.

A lot of trial recruitment occurs through the trusted word of patient’s regular doctor. But if recruitment is not through this channel essentially the deal needs to be sweetened right up front; for essentially the now "business centres" doing the recruitment and the participants who have shifted from a medical altruism perspective into a whats in this for me type of transaction.

And the use of a little cognitive trick.

The participant thinks 2 chances in 3 of getting benefit for their ailment. But a trial like this may have only a 30% chance of success and even if successful high proportions of participants in the intervention arm may not benefit at all. The odds of benefit are not what the participant thinks at all.

Now in practice what happens is exactly what has occurred here. You reduce trial efficacy due to the costs associated with businesses recruiting in pools of low altruism.

Then you get hit by the bus coming the other way.

It turns out the business units produce an excess of participants because you have incentivised for this. It turns out the cognitive trick works too well. And the complex contractual arrangements are not worth the bother of arguing about with the "business units" – so the excess participants are allowed in.

The net result of this is even greater inefficiency; you have increased power accidentally - for no good reason.

The final twist occurs in the market release … over-enrolment … must be a treatment in great demand … must probably work … everything is good.