David Laursen

Webinar - read more and sign up: www.cochrane.org/events/how-t...

On 17 February 2026, Andreas Lundh and Asbjørn Hrobjartsson will host a Cochrane Learning Live webinar about the TACIT tool.

... IN MICE 🐭

jamesheathers.medium.com/in-mice-expl...

Vigtigt med retvisende overskrifter og passende forbehold for ekstrapolering til mennesker.

#JustSaysInMice #InMice #IMus

Many seemingly overlapping terms: MCID, MID, minimally relevant different (MiReDif), smallest effect size of interest (SESOI), smallest worthwhile difference (SWD) ...

Different traditions? Would be nice with a good overview.

Thanks, I'll check it out!

Any specific critical literacy resources from philosophy you would recommend?

Happening TODAY at 3pm GMT 👇

Introduction to INSPECT-SR Training Workshop December An introductory 2-hour online workshop will introduce participants to the INSPECT-SR tool for assessing trustworthiness of randomised controlled...

Have increased capacity for this December INSPECT-SR online training workshop following a successful 1st event today. Book here: www.trybooking.com/uk/FKHV

Recent trial with potential data problems @bmj.com. Great with IPD available for checking.

Helpful/feasible with early standard checks in submission? E.g. onlinelibrary.wiley.com/doi/full/10....) or INSPECT-IPD (in development, www.sciencedirect.com/science/arti..., @jdwilko.bsky.social)

In Danish, it is similar with the word for male cousin (perhaps more in humorous context). E.g., "I saw this weird cousin in the train today ..."

@tweis.bsky.social

Just to clarify our definition: active placebo = similarly looking control + imitating the perceptible side effects of the exp drug + not therapeutic. Agree that standard of care needs to be considered for both/control arm(s), e.g. therapeutically active control.

Example of a trial sequential analysis plot. From: https://ctu.dk/tsa/

What: Webinar on trial sequential analysis (TSA) in meta-analyses
When: 28 Oct 2025 13:00 to 13:45 (CEST)
Where: syddanskuni.zoom.us/j/61110310530

Christian Gunge Riberholt, associate professor at the University of Copenhagen, will talk about TSA and the potential errors of using it.

#MetaAnalysis

Ah, OK! Stopping rules are not my field so forgive me if mistaken. I think active placebos would likely not mask true disease progression itself, but potentially affect "subjective" assessments, e.g. chronic pain, depression, PTSD. (But ethics important re. imitated side effects' acceptability)

Does anyone have any good examples of PPI for stats methodology? I’ve seen a few but they are all related to a clear applied research question, rather than actual methods

NB. Heterogeneity/meta-regression analyses likely imprecise like the main analysis, so absence of evidence != evidence of absence.

It might. Underlying mechanisms probably relate to, e.g., outcome types (patient vs observer), active placebo matching quality, trial design (crossover vs parallel). Heterogeneity not explained by these factors (nor by condition or drug category).

Can you elaborate on phase and trt strategies?

Blinding in randomized clinical trials: imposed impartiality - PubMed Blinding, or "masking," is a crucial method for reducing bias in randomized clinical trials. In this paper, we review important methodological aspects of blinding, emphasizing terminology, reporting, ...

... For mechanisms for bias for to lack of blinding see, e.g.:
pubmed.ncbi.nlm.nih.gov/11879884/
pubmed.ncbi.nlm.nih.gov/21993424/

If unblinding does matter, probably same mechanisms as complete lack of blinding. E.g. for patient-reported outcomes probably response bias (or placebo effect since these are difficult to disentangle), But also changes in co-interventions, compliance, attrition. Don't know for sure. ...

#EpiSky
Maybe #MetaEpiSky?

Impact of active placebo controls on estimated drug effects in randomised trials: a systematic review of trials with both active placebo and standard placebo - Laursen, DRT - 2023 | Cochrane Library Select your preferred language for Cochrane reviews and other content. Sections without translation will be in English.

References:
Within-trial analysis (first study, 2023): www.cochranelibrary.com/cdsr/doi/10....
Between-trial analysis (second study, in press): www.jclinepi.com/article/S089...
Twitter/X thread for first study: x.com/LaursenDavid...

10/10

Perhaps we are at least now more certain about our uncertainty. Additional future trials with both types of placebo controls would be useful ...

Thanks to all my co-authors and especially my main supervisor Asbjørn Hróbjartsson!

9/10

Tricky to interpret these results. Maybe unblinding doesn't matter, maybe the active placebos are not good enough, or maybe they do matter and we just don't have enough data to detect, or maybe our there is some flaw somewhere in the meta-research methods.

8/10

In our papers, we discuss limitations, e.g. for both studies imprecision and heterogeneity, for within-trial analysis external validity, and for between-trial analysis residual confounding.

7/10

Results: Confidence intervals from both studies were wide and compatible with no average impact and important average impact. Within-trial analysis: ROR 0.86, 95% CI 0.70 to 1.08. Between-trial analysis: ROR 0.98, 95% CI 0.77 to 1.24.

6/10

We identified and meta-analysed randomised within-trial comparisons (first study) and observational between-trial comparisons (second study). We analysed ratio of odds ratios: ROR < 1 meaning standard placebo-controlled trials exaggerated the experimental drug effects, e.g. pain improvement.

5/10

Active placebo controls contain ingredients that attempt to imitate the drug side effects (with varying degree of success). Few studies have actually assessed the impact on estimated drug effects when using active placebo vs using standard placebo. We wanted to investigate exactly this.

4/10

Background: Drug trials are often blinded with a placebo control. But: If the drug has noticeable side effects, e.g. dry mouth or sedation, then patients may be able to guess their treatment. Such unblinding been highlighted as a potential issue for opioids, antidepressant, psychedelics etc.

3/10

After years of deliberation, dread, drudgery, detours, despair, delays, and distress, I am glad (and somewhat relieved) to announce our second paper (in press) attempting to tackle the above questions.

www.jclinepi.com/article/S089...

2/10

Lady Justice partially removing her blindfold from one eye

Does unblinding due to side effects lead to bias in placebo-controlled trials? And are active placebos a possible solution? (Spoiler alert: we are not sure.)

#ActivePlacebo #ActivePlacebos #Blinding #Unblinding #Placebo #Bias

1/10

#SundDK #SundPol