Zeigt her Eure negativen Resultate!

12. Juni 2013 von Laborjournal

Sicher eine gute Aktion: Die Open Access-Zeitschrift F1000Research ruft dazu auf, Manuskripte, die negative oder Null-Resultate beschreiben, explizit dort einzureichen. Haben die Editoren sich versichert, dass die jeweiligen „Kein Effekt“-Resultate klaren Fragestellungen und solider experimenteller Arbeit entspringen, veröffentlichen sie die entsprechenden Paper gebührenfrei. Jedenfalls, sofern das Manuskript vor dem 31. August bei F1000Research eingetroffen ist — solange geht vorerst die Aktion.

Warum das eine gute Idee ist, beschreibt F1000Research in seinem Blog selbst sehr gut:

It can be very difficult to get papers presenting negative or null results published.  Many important results from scientific experiments are never published in the traditional peer reviewed literature, but negative and null results present a particular challenge. Despite the fact that many of these experiments are carefully designed and well executed, negative-result papers are regularly turned down by journals simply because they don’t show an exciting new finding.

This is not only a disappointment for the researchers who conducted the work, it’s also damaging to the overall scientific record. This so-called “publication bias” toward positive results makes it appear as though the experiments with negative or null results never happened.

Sometimes the unpublished experiments are obvious next steps in elucidating a particular biological mechanism, making it likely that other researchers will try the same thing, not realizing that someone else already did the work. This is a waste of time and money.

On other occasions, the positive results that are published are the exception: they could have been specific to a narrow set of conditions, but if all the experiments that didn’t work are not shown, these exceptional cases now look like the only possible result. This is especially damaging when it comes to drug development and medical research, where treatments may be developed based on an incomplete understanding of research results.

Interessanterweise schildert unsere Lab Times-Eule gerade in ihren letzten „Observations of the Owl“ unter der Überschrift „Important Negatives“ genau solch einen Fall. Und da dieser das große Dilemma nicht-publizierter negativer Resultate besonders schön illustriert, zitieren wir ihre Geschichte hier noch einmal:

A long time ago, my friend Sparrowhawk and I were working in some forest lab in what you humans call Southern Norway. Sparrowhawk was in the Department of Medicine, Division of Wing Orthopaedics, and I was in the Department of Muscle Physiology. One day, we were discussing the possible molecular mechanisms that trigger the rare Progressive Flight Fatigue Syndrome (PFFS): a terrible disorder affecting mostly young birds, which starts with difficulties in coping with longer flights and finally ends up with complete loss of wing muscle function — and death.

The point is not, as you might think, that their muscle mass must inevitably shrink. The exact opposite is, in fact, the case: the muscles gradually lose their power and functionality because they get thicker and thicker and thicker. They just do not stop growing — and thereby finally kill the affected individuums. (This would be the ultimate for some of your unscrupulous poultry farmers in one or another perverse dream, wouldn’t it?)

Anyway, we considered the possibility that in those poor guys the bird insulin-like growth factor 1 (BIGF1) somehow overshoots and, hence, constantly forces the muscles to keep on growing and growing. Of course, we wanted to test the idea. And thus, we collected blood samples from every bird showing the first signs of developing PFFS. As mentioned, these were rare, but you humans just cannot imagine how even seemingly Herculean tasks can actually be tackled with a well-oiled network of feathery scientists in the background.

When we finally had sufficient material at hand, we checked everything: BIGF1 levels, enzymes of BIGF1-synthesis and -degradation, BIGF1-inhibiting and BGIF1-releasing enzymes, expression of BIGF1-responsive enzymes… We repeated all those analyses three times — but nothing! In all PFFS birds, the whole “BIGF1-world” was completely indistinguishable from their healthy fellows.

Okay, it was not what we had expected but, nevertheless, we thought it was important to communicate the results in the literature. After all, BIGF1 is one of the most important muscle growth factors in birds and, thus, certainly a prime candidate to cause wing muscle overgrowth, when going wild. But now, our data had shown without any doubt that BIGF1 didn’t play even the slightest role in the biochemical pathology of PFFS.

We thought that many researchers might arrive at the same idea and attempt to do what we had already done. What a waste of time, money and careers; these would obviously be at stake if they weren’t informed of our results in time!

Thus, Sparrowhawk and I hurried to write up the manuscript. But what happened after sending it off hit us by surprise, like a hammer — and repeatedly so. Be it Bird Hormones, Wings, Flight Metabolism or a sheer dozen of other journals, they all rejected its publication – not based on merit or methodology but on the grounds that the journals “do not publish negative results”.

When I left research a few years later the paper still hadn’t been published and I rapidly lost track of the PFFS field. Nevertheless, when dusting my cave I sometimes look into the old manuscript, marvel at all the thinking and work we invested, especially the pretty hand-drawn graphs, sadly think “what a waste”, angrily almost throw it away… but rescue it at the last minute to sentimentally put it back in my files.

Hopefully, after so many years, somebody has repeated the results — and finally succeeded in publishing them.

Womit nun hoffentlich klar geworden ist, wie und warum es wichtig ist, solche negativen Ergebnisse den Kollegen mitzuteilen.

Vielleicht bewirkt die F1000Research-Aktion ja tatsächlich ein Umdenken — und verhilft am Ende soliden negativen Ergebnissen tatsächlich zu dem Stellenwert, den sie verdienen. Was natürlich umso besser funktioniert, je mehr Leute mitmachen. Also, holt sie raus aus euren Schubladen, die vielen „Leider-kein-Effekt“-Studien! Ihr wisst jetzt, wohin ihr sie schicken könnt.

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