Evidence map›Paper›PMID 33239053›Full record

ArticleTrials2020

Update to the FOCUS, AFFINITY and EFFECTS trials studying the effect(s) of fluoxetine in patients with a recent stroke: statistical analysis plan for the trials and for the individual patient data meta-analysis.

Gillian Elizabeth Mead, Catriona Graham, Laurent Billot, Per Näsman, Erik Lundström, Steff Lewis, Graeme J Hankey, Maree L Hackett, John Forbes, Martin Dennis and 1 more

Registry-linked trialOpen access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Trials, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02683213 (Establishing the Effect), which is not on this map. Cited by 3 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed, 2 pooled it
0.2field-weighted citation impact, top 38% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT02683213 phase3completednot on this map

Establishing the Effect(s) and Safety of Fluoxetine Initiated in the Acute Phase of Stroke

TypeinterventionalSponsorKarolinska InstitutetRan2014 to 2020Enrolled1,500ConditionsStrokeArmsFluoxetine, Placebo
3 · Its place in the literature

Who cites it

3 citing papers in PubMed, 2 syntheses or guidelines pooled it, 4 citations in OpenAlex.

  1. Individual patient data meta-analysis of the effects of fluoxetine on functional outcomes after acute stroke.International journal of stroke : official journal of the International Stroke Society · 2024
    Pooled it
  2. Selective serotonin reuptake inhibitors (SSRIs) for stroke recovery.The Cochrane database of systematic reviews · 2021
    Pooled it
  3. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

11 authors at 7 institutions in 4 countries.

Gillian Elizabeth MeadUsher Institute, University of Edinburgh, , Room S1642, Royal Infirmary, Little France Crescent, Edinburgh, EH16 4SA, UK. gillian.e.mead@ed.ac.uk.
Catriona GrahamWelcome Trust Clinical Research Facility, Western General Hospital, Crewe Road, Edinburgh, EH4 2XU, UK.
Laurent BillotThe George Institute for Global Health, University of Sydney, Sydney, NSW, Australia.
Per NäsmanCenter for Safety Research, KTH Royal Institute of Technology, Stockholm, Sweden.
Erik LundströmDepartment of Neuroscience, Neurology, Uppsala University, Uppsala, Sweden.
Steff LewisUniversity of Edinburgh, Level 2, NINE Edinburgh BioQuarter, 9 Little France Road, Edinburgh, EH16 4UX, UK.
Graeme J HankeyMedical School, Faculty of Health and Medical Sciences, The University of Western Australia, Crawley, WA, Australia.
Maree L HackettThe George Institute for Global Health, University of Sydney, Sydney, NSW, Australia.ORCID http://orcid.org/0000-0003-1211-9087
John ForbesHealth Research Institute, University of Limerick, Limerick, Ireland.
Martin DennisCentre for Clinical Brain Sciences, University of Edinburgh, Chancellor's Building, Little France Crescent, Edinburgh, EH16 4SA, UK.
FOCUS, AFFINITY and EFFECTS trialists
The University of Sydney · AUUppsala University · SEEdinburgh Royal Infirmary · GBThe University of Western Australia · AUUniversity of Edinburgh · GBUniversity of Limerick · IEWestern General Hospital · GB

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundThree large trials of fluoxetine for stroke recovery (FOCUS (fluoxetine or control under supervision), AFFINITY (the Assessment oF FluoxetINe In sTroke recovery) and EFFECTS (Efficacy oF Fluoxetine-a randomisEd Controlled Trial in Stroke)) have been collaboratively designed with the same basic protocol to facilitate an individual patient data analysis (IPDM). The statistical analysis plan for the three individual trials has already been reported in Trials, including a brief description of the IPDM. In this protocol, we describe in detail how we will perform the IPDM. METHODS/

designData from EFFECTS and AFFINITY will be transferred securely to the FOCUS statistician, who will perform a one-stage IPDM and a two-stage IPDM. For the one-stage IPDM, data will be combined into a single data set and the same analyses performed as described for the individual trials. For the two-stage IPDM, the results for the three individual trials will be combined using fixed effects meta-analyses. The primary and secondary outcome domains for the IPDM are the same as for individual trials. We will also perform analyses according to several subgroups including country of recruitment, ethnicity and trial. We will also explore the effects of fluoxetine on our primary and secondary outcomes in subgroups defined by combinations of characteristics. We also describe additional research questions that will be addressed using the combined data set, and published subsequently, including predictors of important post-stroke problems such as seizures, low mood and bone fractures. DISCUSSION: An IPDM of our three large trials of fluoxetine for stroke recovery will allow us to provide the most precise estimates of any risks and benefits of fluoxetine vs placebo, to detect reliably a smaller overall effect size than those detectable by the individual trials, to better determine the effects of fluoxetine vs placebo in subgroups of patients and outcomes and to broaden the generalisability of the results. Also, we may identify differences in treatment effects between studies.

trial registrationFOCUS: ISRCTN ISRCTN83290762 . Registered on 23 May 2012. EudraCT 2011-005616-29 . Registered on 3 February 2012. AFFINITY: Australian New Zealand Clinical Trials Registry ACTRN12611000774921 . Registered on 22 July 2011. EFFECTS: ISRCTN ISRCTN13020412 . Registered on 19 December 2014. ClinicalTrials.gov NCT02683213 . Registered on 2 February 2016. EudraCT 2011-006130-16 . Registered on 8 August 2014.

Indexed as

Brain IschemiaData Interpretation, StatisticalStrokeAgedFemaleFluoxetineHumansMaleMeta-Analysis as TopicRandomized Controlled Trials as TopicRecovery of FunctionResearch DesignTreatment OutcomeFluoxetineAFFINITYEFFECTSFOCUSIndividual patient data meta-analysisRecoveryStroke

Identifiers

PMID33239053
PMCPMC7687683
OpenAlexW3109592235

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.