Recently in a train station book shop I stood gaping in astonishment in front of a thematically highly specialized book display. It was the bowels-brain table. The books piled up on it promised enlightenment about how the bowel and in particular its contents influence us – yes – how, they verily steer our emotions. A selection of book titles: “Shit-Wise – How a Healthy Intestinal Flora Keeps us fit”; “Bowels heal brain heal body”; “Happiness begins in the bowels”, or “The second brain – How the bowels influence our mood, our decisions and our feeling of wellbeing”. Newspapers, magazines and the internet can also tell us this. The wrong bowel bacteria make us depressive – but the right ones make us happy … which is why yogurt helps against depression. Continue reading
- Let’s get this out of the way: Reproducibility is a cornerstone of science: Bacon, Boyle, Popper, Rheinberger
- A ‘lexicon’ of reproducibility: Goodman et al.
- What do we mean by ‘reproducible’? Open Science collaboration, Psychology replication
- Reproducible – non reproducible – A false dichotomy: Sizeless science, almost as bad as ‘significant vs non-significant’
- The emptiness of failed replication? How informative is non-replication?
- Hidden moderators – Contextual sensitivity – Tacit knowledge
- “Standardization fallacy”: Low external validity, poor reproducibility
- The stigma of nonreplication (‘incompetence’)- The stigma of the replicator (‘boring science’).
- How likely is strict replication?
- Non-reproducibility must occur at the scientific frontier: Low base rate (prior probability), low hanging fruit already picked: Many false positives – non-reproducibility
- Confirmation – weeding out the false positives of exploration
- Reward the replicators and the replicated – fund replications. Do not stigmatize non-replication, or the replicators.
- Resolving the tension: The Siamese Twins of discovery & replication
- Conclusion: No scientific progress without nonreproducibility: Essential non-reproducibility vs . detrimental non-reproducibility
- Further reading
It is for good reason that researchers are the object of envy. When not stuck with bothersome tasks such as grant applications, reviews, or preparing lectures, they actually get paid for pursuing their wildest ideas! To boldly go where no human has gone before! We poke about through scientific literature, carry out pilot experiments that surprisingly almost always succeed. Then we do a series of carefully planned and costly experiments. Sometimes they turn out well, often not, but they do lead us into the unknown. This is how ideas become hypotheses; one hypothesis leads to those that follow, and voila, low and behold, we confirm them! In the end, sometimes only after several years and considerable wear and tear on personnel and material, we manage then to weave a “story” out of them (see also). Through a complex chain of results the story closes with a “happy end”, perhaps in the form of a new biological mechanism, but at least as a little piece to fit the puzzle, and it is always presented to the world by means of a publication. Sometimes even in one of the top journals. Continue reading
Based on research, mainly in rodents, tremendous progress has been made in our basic understanding of the pathophysiology of stroke. After many failures, however, few scientists today deny that bench-to-bedside translation in stroke has a disappointing track record. I here summarize many measures to improve the predictiveness of preclinical stroke research, some of which are currently in various stages of implementation: We must reduce preventable (detrimental) attrition. Key measures for this revolve around improving preclinical study design. Internal validity must be improved by reducing bias; external validity will improve by including aged, comorbid rodents of both sexes in our modeling. False-positives and inflated effect sizes can be reduced by increasing statistical power, which necessitates increasing group sizes. Compliance to reporting guidelines and checklists needs to be enforced by journals and funders. Customizing study designs to exploratory and confirmatory studies will leverage the complementary strengths of both modes of investigation. All studies should publish their full data sets. On the other hand, we should embrace inevitable NULL results. This entails planning experiments in such a way that they produce high-quality evidence when NULL results are obtained and making these available to the community. A collaborative effort is needed to implement some of these recommendations. Just as in clinical medicine, multicenter approaches help to obtain sufficient group sizes and robust results. Translational stroke research is not broken, but its engine needs an overhauling to render more predictive results.
Read the full article at the Publishers site (STROKE/AHA). If your library does not have a subscription, here is the Authors Manuscript (Stroke/AHA did not allow me to even pay for open access, as it is ‘a special article…’).
Using metaanalysis and computer simulation we studied the effects of attrition in experimental research on cancer and stroke. The results were published this week in the new meta-research section of PLOS Biology. Not surprisingly, given the small sample sizes of preclinical experimentation, loss of animals in experiments can dramatically alter results. However, effects of attrition on distortion of results were unknown. We used a simulation study to analyze the effects of random and biased attrition. As expected, random loss of samples decreased statistical power, but biased removal, including that of outliers, dramatically increased probability of false positive results. Next, we performed a meta-analysis of animal reporting and attrition in stroke and cancer. Most papers did not adequately report attrition, and extrapolating from the results of the simulation data, we suggest that their effect sizes were likely overestimated. Continue reading
This has been a week chock-full of bias! First nature ran a cover story on it, with an editorial, and a very nice introduction into the subject by Regina Nuzzo. Then Malcolm Macleod and colleagues published a perspective in Plos Biology demonstrating limited reporting of measures to reduce the risk of bias in life sciences publications, and that there may be an inverse correlation between journal rank or prestige of the University from which the research originated and presence of measures to prevent bias. At the same time Jonathan Kimmelman’s group came out with a report in eLife in which they meta-analytically explored preclinical studies of an anticancer drug (sunitinib) to demonstrate that only a fraction of drugs that show promise in animals end up proving safe and effective in humans, partly because of design flaws, such as lack of prevention of bias, and partly due to positive publication bias. Both articles resulted in a worldwide media frenzy, including coverage by Nature and the lay press, here is an example from the Guardian. Retraction Watch interviewed Jonathan, while Malcolm spoke on BBC4.
Eine Sendung des Deutschlandfunk (ausgestrahlt 20.9.15) von Martin Hubert. Aus der Ankündigung: ‘Biomediziner sollen in ihren Laboren unter anderem nach Substanzen gegen Krebs oder Schlaganfall suchen. Sie experimentieren mit Zellkulturen und Versuchstieren, testen gewollte Wirkungen und ergründen ungewollte. Neuere Studien zeigen jedoch, dass sich bis zu 80 Prozent dieser präklinischen Studien nicht reproduzieren lassen.’ Hier der Link zum Audiostream bzw. zum Transkript.
(German only, sorry!)