BJP issues new policy on SABV

September 4, 2019

The British Journal of Pharmacology has been issuing a barrage of initiatives over the past few years that are intended to address numerous issues of scientific meta-concern including reproducibility, reliability and transparency of methods. The latest is an Editorial on how they will address current concerns about including sex as a biological variable.

Docherty et al. 2019 Sex: A change in our guidelines to authors to ensure that this is no longer an ignored experimental variable. https://doi.org/10.1111/bph.14761 [link]

I’ll skip over the blah-blah about why. This audience is up to speed on SABV issues. The critical parts are what they plan to do about it, with respect to future manuscripts submitted to their journal. tldr: They are going to shake the finger but fall woefully short of heavy threats or of prioritizing manuscripts that do a good job of inclusion.

From Section 4 BJP Policy: The British Journal of Pharmacology has decided to rectify this neglect of sex as a research variable, and we recommend that all future studies published in this journal should acknowledge consideration of the issue of sex. In the ideal scenario for in vivo studies, both sexes will be included in the experimental design. However, if the researcher’s view is that sex or gender is not relevant to the experimental question, then a statement providing a rationale for this view will be required.

Right? Already we see immense weaseling. What rationales will be acceptable? Will those rationales be applied consistently for all submissions? Or will this be yet another frustrating feature for authors in which our manuscripts appear to be rejected on grounds that other papers published seem to suffer from?

We acknowledge that the economics of investigating the influence of sex on experimental outcomes will be difficult until research grant‐funding agencies insist that researchers adapt their experimental designs, in order to accommodate sex as an experimental variable and provide the necessary resources. In the meantime, manuscripts based on studies that have used only one sex or gender will continue to be published in BJP. However, we will require authors to include a statement to justify a decision to study only one sex or gender.

Oh a statement. You know, the NIH has (sort of, weaselly) “insisted”. But as we know the research force is fighting back, insisting that we don’t have “necessary resources” and, several years into this policy, researchers are blithely presenting data at conferences with no mention of addressing SABV.

Overall sex differences and, more importantly, interactions between experimental interventions and sex (i.e., the effect of the intervention differs in the two sexes) cannot be inferred if males and females are studied in separate time frames.

Absolutely totally false. False, false, false. This has come up in more than one of my recent reviews and it is completely and utterly, hypocritically wrong. Why? Several reasons. First of all in my fields of study it is exceptionally rare that large, multi-group, multi-sub-study designs (in single sex) are conducted this way. It is resource intensive and generally unworkable. Many, many, many studies include comparisons across groups that were not run at the same time in some sort of cohort balancing design. And whaddaya know those studies often replicate with all sorts of variation across labs, not just across time within lab. In fact this is a strength. Second, in my fields of study, we refer to prior literature all the time in our Discussion sections to draw parallels and contrasts. In essentially zero cases do the authors simply throw up their hands and say “well since nobody has run studies at the same time and place as ours there is nothing worth saying about that prior literature”. You would be rightfully laughed out of town.

Third concern: It’s my old saw about “too many notes“. Critique without an actual reason is bullshit. In this case you have to say why you think the factor you don’t happen to like for Experimental Design 101 reasons (running studies in series instead of parallel) has contributed to the difference. If one of my peer labs says they did more or less the same methods this month compared to last year compared to five years ago…wherein lies the source of non-sex-related variance which explains why the female group self-administered more cocaine compared with the before, after and in between male groups which all did the same thing? And why are we so insistent about this for SABV and not for the series of studies in males that reference each other?

In conscious animal experiments, a potential confounder is that the response of interest might be affected by the close proximity of an animal of the opposite sex. We have no specific recommendation on how to deal with this, and it should be borne in mind that this situation will replicate their “real world.” We ask authors merely to consider whether or not males and females should be physically separated, to ensure that sight and smell are not an issue that could confound the results, and to report on how this was addressed when carrying out the study. Obviously, it would not be advisable to house males and females in different rooms because that would undermine the need for the animals to be exposed to the same environmental factors in a properly controlled experiment.

NO SHIT SHERLOCK!

Look, there are tradeoffs in this SABV business when it comes to behavior studies, and no doubt others. We have many sources of potential variance that could be misinterpreted as a relatively pure sex difference. We cannot address them all in each and every design. We can’t. You would have to run groups that were housed together, and not, in rooms together and not, at times similar and apart AND MULTIPLY THAT AGAINST EACH AND EVERY TREATMENT CONDITION YOU HAVE PLANNED FOR THE “REAL” STUDY.

Unless the objective of the study is specifically to investigate drug‐induced responses at specific stages of the oestrous cycle, we shall not require authors to record or report this information in this journal. This is not least because procedures to determine oestrous status are moderately stressful and an interaction between the stress response and stage of the oestrous cycle could affect the experimental outcome. However, authors should be aware that the stage of the oestrous cycle may affect response to drugs particularly in behavioural studies, as reported for actions of cocaine in rats and mice (Calipari et al., 2017; Nicolas et al., 2019).

Well done. Except why cite papers where there are oestrous differences without similarly citing cases where there are no oestrous differences? It sets up a bias that has the potential to undercut the more correct way they start Section 5.5.

My concern with all of this is not the general support for SABV. I like that. I am concerned first that it will be toothless in the sense that studies which include SABV will not be prioritized and some, not all, authors will be allowed to get away with thin rationales. This is not unique to BJP, I suspect the NIH is failing hard at this as well. And without incentives (easier acceptance of manuscripts, better grant odds) or punishments (auto rejects, grant triages) then behavior won’t change because the other incentives (faster movement on “real” effects and designs) will dominate.

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