One of the worst kinds of unethical research practice is to fail to publish results after a prospective study.

Parents consent to research for altruistic motives, in the belief that their baby’s participation will help the care of other, future, babies. Failing to carry through and publish, or at the very least, make results publicly available on the registration website, is an abuse of that consent. It is fraudulent to ask for consent for a prospective study and then to hide the results because they are not what you wanted to find.

This is one of the major reasons behind the mandatory registration of prospective research on publicly available registers. All prospective research, including essential details such as eligibility, sample size, interventions, and primary outcomes, must be registered, prior to enrolling patients. This is an important safeguard against investigators changing those details, without an openly available rationale. Clearly, sample sizes may change (almost always decrease) because of unforeseen circumstances, eligibility criteria may be adjusted, and even major outcomes may be changed. However, the initially planned primary outcome must always be reported, even if it is adjusted prior to analysis of the results. Any change in outcomes reported, or additional outcomes, after the results have been analyzed must also be clearly reported as being post hoc, and are always only hypothesis generating.

A recent study of a relatively non-invasive test of lung maturity (testing the L:S ratio on gastric aspirates (GAS), from a gastric tube that was inserted for clinical reasons) was performed, and some results have just been published by the clinical investigators. Heiring C, et al. Predicting Surfactant Need at Birth: Failed Validation of a Bedside Method Using Gastric Aspirates. Acta Paediatr. 2025. The method failed to adequately predict the need for surfactant… as far as we know.

This was a 4 centre study from Denmark among infants of <30 weeks gestation less than 45 minutes of age, who had not yet had surfactant. The primary outcome as noted on the registration page was the L:S ratio on the samples, the registration page notes : “The primary objective is to measure the L/S-ratio in fresh GAS using the AIMI 1.0/2.0 L/S POC Device and compare the L/S-ratio with the need for surfactant treatment aiming to validate the previously defined cut-off L/S-ratio for surfactant treatment and to determine if the cut-off L/S ratio needs adjustment before starting FAST 2 RCT”.

Of note, this is a really good acronym! It comes from the methodology used and the intervention expected Fourier trAnsform infra-red spectroscopy guided Surfactant Therapy. Or maybe, Fast Assessment of Surfactant deficiency to speed up Treatment.

Having performed the study, consented parents, and submitted the samples for testing, the patent holders who work with the company are refusing to allow publication of the pre-defined outcome. As the title of this post states, those partners in this study are clearly acting unethically, they are abusing the trust of the families who consented to the study.

Fortunately, we know about this because of the courage of the clinical investigators, and of the Editors of Acta Paediatrica, who have written and published the above article describing the study, documenting the dispute, and noting “disagreements over how the study findings should be reported and which findings to include. Specifically, the laboratory group proposed an unbalanced emphasis on lecithin (DPPC) alone as a predictor of surfactant treatment, based on post hoc analyses using an open dataset outside the framework of the agreed-upon protocol”. As I mentioned above, I don’t think that post-hoc analyses should be banned, but it is essential to focus on the results of the primary, pre-planned analyses. Anything that results from an inspection of the results, after they have been collected, is inherently unreliable, and must be submitted to further independent testing.

It appears that the company has “swivelled” and an abstract at the recent PAS-meeting appears to be reporting a study using the same device, but now discusses its use for predicting prolonged respiratory support (>6 h duration), not surfactant requirement. Firstly, I would caution the researchers at the Mayo clinic to ensure that they have a legally binding agreement to publish the results, especially the pre-specified primary outcome, otherwise they may find themselves in the same dilemma as the Danish researchers. Secondly, what is the purpose of this? How does that help? what would you do about it? The abstract doesn’t have enough detail to explain potential uses, but hopefully the investigators will make that clear in the future.

It is not unusual for a company which has invested in development of a new drug/technique/machine, and then finds it not to be very useful for the initial indication, to find something posthoc and swivel to that as an indication. It is an understandable reaction, one does not wish to lose the investment that has previously been made, and finding another indication might save the family jewels. One positive example of this is sildenafil, which was initially being developed as an angina treatment (where it seems to be effective, but may cause profound hypotension if the patient then takes their nitrates), but the company, post hoc, noted the frequent side effect of erections! And we all know what followed.

Research ethics approvals should include a legally binding agreement that the results will be submitted for publication, and that the publication must report the approved primary outcome, which must be identified as such. I don’t believe that is the case in many jurisdictions, but it should become the norm, to avoid situations such as this one.