Phase I results ‘less likely to be published’

The French and US researchers claim to have found clear evidence of publication bias in their study, which appears in the journal PLoS Medicine​ (February 2009).

Evelyne Decullier and colleagues from the University of Lyon, France, and Mayo Clinic in the US studied the outcomes and fate of 444 pharmaceutical trials approved by research ethics committees in France.

They found that just 17 per cent of 140 Phase I trials had been published, compared to 43 per cent of later-stage (Phase II to IV) studies.

In fact. for around half of the Phase I trials, the results had not been made publicly available in any form. The authors said that confidentiality was the main reason given for not disseminating the data.

Phase I results are clearly “far less disseminated​” than studies in other phases, the team concludes. But they argue the converse should be the case as Phase I studies constitute the first exposure to a new drug by human subjects, and in many cases are conducted in otherwise healthy subjects.

The researchers also cite the Phase I trial of Tegenero’s TGN1412 in Northwick Park Hospital, UK, which left six men fighting for their lives after suffering serious adverse reactions. That outcome “might have been avoided had the results of a previous unpublished trial of a similar antibody been known​,” they assert.

"The testing of new pharmaceuticals on humans is approved by ethics committees based on the assumption that the inherent risks of trial participation are balanced by the benefit of new scientific knowledge for society​,” said Decullier.

“If this knowledge from Phase I remains hidden, then any potential risk incurred by trial participation is excessive and could endanger human lives.​"

In recent years drugmakers have made efforts to become more transparent, stung by research which found that the results of trials in which a new drug outperforms a standard treatment were more likely to be published than those in which the drug performed badly or had side effects.

Many companies now operate their own trial databases and in the US, for example, are required submit details of all studies to the ClinicalTrials.gov website. However, Phase I trials are exempted.

“All clinical trials - including Phase I - should be publicly registered at inception and their results disseminated in a timely manner​,” conclude the researchers.