Neonatal Research

A story published in the PNEJM from a mother of a patient with epilepsy that was very difficult to treat who is also a physician, as is the father. Their boy eventually had seizure surgery, more than once.

She ends the piece with this quote:

“Is it easier or harder to have a sick child when both parents are doctors?” But this is the wrong question. There is no hard, no easy. Only fear and love, panic and relief, shaking and not shaking.

(the ‘shaking’ refers to her son’s seizures).

Annie and I have been asked the same question many times, about our experiences as parents in the NICU. I would echo the sentiment of this author, it was no harder, no easier, it is hard for everyone who has a critically ill child. There was fear and love, panic and relief, and eventually, for us, resolution and acceptance.

I have mentioned Richard Lehman’s weekly journal review here before. This week’s edition starts with a critique of a trial published in the PNEJM, funded by a company that makes a new antiviral, the results show a reduction in virus shedding in adults with Herpes randomized to get the new drug. Richard Lehman asks

Does this reduction in shedding actually have any clinical significance? At what point should the FDA release it for use on the general population? What should the end points be, and what should be the duration of the next trial? I think these issues should be a matter of public debate, and not a matter for AiCuris [the manufacturer] to decide. Same with all new drugs. It is we who will be using them, we who will pay for them, and we who stand to be harmed by them.

Exactly. There are too many trials with surrogate end-points of unknown or dubious clinical significance, this new trial publication doesn’t give any evidence that the patients were actually better off with the new drug.

Which leads me to the final two papers in the Lancet series on improving quality and reducing waste in research.

Glasziou P, Altman DG, Bossuyt P, Boutron I, Clarke M, Julious S, Michie S, Moher D, Wager E: Reducing waste from incomplete or unusable reports of biomedical research. The Lancet 2014, 383(9913):267-276.
Chan A-W, Song F, Vickers A, Jefferson T, Dickersin K, Gøtzsche PC, Krumholz HM, Ghersi D, van der Worp HB: Increasing value and reducing waste: Addressing inaccessible research. The Lancet 2014, 383(9913):257-266.

Both of them again have suggestions for improvement, and the article by Paul Glasziou, in particular I find very insightful; journal editors should all take note! (and reviewers like me.)

This new Australian publication asks the question  in its title that many of us are asking. (Cundy TP, Gardener GJ, Andersen CC, Kirby CP, McBride CA, Teague WJ: Fetoscopic endoluminal tracheal occlusion (feto) for congenital diaphragmatic hernia in australia and new zealand: Are we willing, able, both or neither? Journal of Paediatrics and Child Health 2014).

In case you are wondering, this means doing an amnioscopy, and then doing a tracheoscopy on the fetus to deposit a balloon that occludes the trachea. Not a straightforward procedure! Then in some protocols a second procedure before term to remove the balloon. The article that I cited reviews the literature and notes that there are now 9 reports of various trials including 4 very small RCTs. Recent data show much less prematurity than the older publications, as techniques have evolved. The FETENDO technique does look like there is  a good chance that it decreases mortality in the most severe cases.

In answer to my own question, posed in the title, I don’t think we are ready for widespread adoption, but ongoing studies will be important. I think that perhaps the technique should be available for very high risk cases who are not willing to be randomized, but who will be evaluated prospectively, as an ‘innovative therapy’.

My recent post about Annie Janvier’s paper, which described the experiences of families who had an antenatal diagnosis of trisomy 13 or trisomy 18 generated a lot of comments (at least a lot for my blog). Many of them are parents recounting their own experiences, and how they illustrate or differ from those described by Guon et al. If you are interested a few brief minutes of reading is quite educational.

I also had a comment (verbal) from Annie, who noted that I described the study subjects as families who had ‘decided not to terminate the pregnancy’. She scolded me (gently) for using that phrase as a negative, rather than stating that they ‘continued the pregnancy’. I certainly didn’t mean to be negative, but she is right that language is powerful, and the automatic assumption that the default response to such a diagnosis is termination, is the source of many of the problems that families may experience. So my apologies.

Also 2 of the responses to the post noted that there is now an international alliance to aid and support families (International Trisomy 13/18 Alliance
http://www.internationaltrisomyalliance.com): as well as the web site and the newsletter, they have produced a series of educational booklets for families, including one for families who experience a prenatal diagnosis (which you can find on this page). In addition to being factually accurate, the booklets are written by families so they give a much more complete description of family experiences.