The need for negative trials.

It is rarely that I want to congratulate the editors of large journals, but this is one of those days. For they have published a large trial that showed that there was no difference in transition between long chain fatty acids and a placebo (paraffin oil) in preventing the transition to psychosis.

yoi160077f2

To our knowledge, this is the first randomized, placebo-controlled, multicenter clinical trial to test the efficacy of long-chain ?-3 PUFAs in preventing transition to psychosis in young people at UHR for psychosis. Although ?-3 PUFAs were well tolerated, they did not demonstrate an advantage over placebo in the prevention of psychosis at 6- or 12-month follow-up evaluations. Secondary outcome measures of psychiatric symptoms and functioning tended to favor the placebo group. This outcome is difficult to explain other than as a chance finding. The results represent a clear failure to replicate the earlier single-center trial.

There are two factors that the trial needs to consider. the first is that they did a power calculation with a 15% transition to psychosis rate and a 13% difference: the results in both groups were a third of this. The second is that both groups that adhered with this treatment did very well.

yoi160077f3

It may be that the paraffin oil was not a placebo. It is much more likely that the adherent group got more psychosocial input and thus had a lower transition rate.

The reason we spend money on controlled trials is not to confirm the previous trials. It is discomfirm them: it is to demonstrate that the new treatment is better than the best available care.

And adding long chain fats fails that test. We need more papers published like this.