🔥 💥Late-Breakers |COBRA RCT
1-day of antibiotic treatment after adequate endoscopic biliary drainage is non-inferior to 4-7 days in adults with acute cholangitis.
💡 Shorter is better+source control
Practice-changing? #ESCMIDGlobal2026 #idsky

Thank you! I completely agree, hence why reporting individual components separately is important. But I don't think we've seen this theoretical concern bear out in real trials in ID yet (granted, n is still very low so far for trials using DOOR as primary outcome).

Nice presentation from @seanong.bsky.social about DOOR/Radar at #ESCMIDGlobal2026

My main worry is lower ranked components dominating

Sarah Walker discussed this issue in her excellent Bradford Hill lecture (recording in link)

How Do We Win? The GAME CHANGER Trial Erin K. McCreary, PharmD (1), Ahmad Mourad, MD MHS (2, 3)

The 3rd and 4th commentaries on recent ID trials are up on the CLARITY website (we aim to publish in depth reviews of important ID stuies).

This time looking at the GAMECHANGER trial:
clarityinitiative.org/commentaries...

@erinmccreary.bsky.social with Ahmad Mourad

@gurujosh.bsky.social

#IDSky

Navigating the Challenges in Staphylococcus aureus Bloodstream Infection: A Practical Guide to Management

New article about how to manage Staphylococcus aureus bacteremia. Led by Hadar Mudrik-Zohar. Includes @seanong.bsky.social @drtoddlee.bsky.social
#IDSky #SNAP_trial

www.sciencedirect.com/science/arti...

#IDSky @steventong.bsky.social @gurujosh.bsky.social @angelahuttner.bsky.social @cmicomms.bsky.social

Breaking down the Desirability of Outcome Ranking (DOOR): unpacking the methodology behind the Dalbavancin as an Option for Treatment of Staphylococcus aureus Bacteremia (DOTS) trial Desirability of Outcome Ranking (DOOR) outcomes such as the primary outcome of the DOTS (Dalbavancin as an Option for Treatment of Staphylococcus aureus Bacteremia) trial can improve statistical effic...

Our first published commentary on the DOTS trial explains the use of the DOOR outcome and discusses the benefits and drawbacks associated with using this outcome.

www.cmi-comms.org/article/S295...

We will publish regular commentaries on new RCTs in ID/Micro, with a focus on methodologic aspects of these studies. A course focused on clinical trials design and methodology is in the works and will run Nov 2026; keep a look out for that. Read more here: doi.org/10.1016/j.cm...

Clarity Initiative Clinical Literature Appraisal and Research education in InfecTious diseases

A group of ID clinical researchers passionate about clinical research and evidence appraisal has just launched the CLARITY initiative (clarityinitiative.org), which aims to improve the generation and interpretation of evidence in ID and Microbiology.

Making Sense of Hierarchical Composite End Points in Randomized Clinical Trials—A Primer for Infectious Diseases Clinicians and Researchers Hierarchical composite end points (HCEs) are increasingly being used in infectious diseases research. In this review aimed at educating the clinical reader

This article is a companion piece to our previous review on hierarchical composite endpoints (HCEs) (doi.org/10.1093/cid/...), where we provided a conceptual overview of HCEs and explained the different analytic methods and possible target parameters associated with their use.

Comparing different methods for analyzing hierarchical composite endpoints: two illustrative case studies with post-hoc analyses of the BALANCE and CAMERA2 randomized clinical trials. Hierarchical composite endpoints (HCEs) are increasingly being used in infectious disease research. In this paper, we illustrate different methods for analyzing HCEs in post-hoc analyses of the BALANC...

Our new paper in @cmijournal.bsky.social:

www.clinicalmicrobiologyandinfection.org/article/S119...

We use the BALANCE and CAMERA2 trials as case studies to illustrate the use of the different methods available for analysis of hierarchical composite endpoints.

#IDSky @steventong.bsky.social

The draft for the 2026 IDSA/ESCMID clinical practice guidelines on 𝘚. 𝘢𝘶𝘳𝘦𝘶𝘴 bacteraemia is now available for public consultation. Get your copy of the manuscript and submit your feedback before 15 December 2025.

https://ow.ly/HZao50XwVYg

#IDSky #clinmicro

Thanks Paul!

@seanong.bsky.social is giving his PhD oration today at 12.30pm AEDT. If you are free, you will learn heaps about clinical trials in infectious diseases. It's been an incredible PhD journey!

unimelb.zoom.us/j/8944229688...

@thedohertyinst.bsky.social

Accounting for non-adherence to assigned antibiotic treatment duration for bloodstream infection (BALANCE): a post-hoc analysis of a randomised clinical trial Non-adherence in BALANCE was significantly associated with a range of important prognostic factors, which might have introduced bias. Causal inference methods addressing this bias showed a consistent ...

New Research

Accounting for non-adherence to assigned antibiotic treatment duration for bloodstream infection (BALANCE): a post-hoc analysis of a randomised clinical trial

www.thelancet.com/journals/lan...

Whoops, thanks for catching that! You're right. Really wish BlueSky had an edit function now...

Thanks a lot Jonathan!!

10/ Our work provides an illustrative example of how statistical methods can obtain adjusted effect estimates in the setting of non-adherence. Investigators should consider the potential impact of protocol non-adherence on their trial results and conduct relevant analyses specific to their context.

9/ Our analyses show that non-adherence did not affect the internal validity of BALANCE's results, and that 7-day antibiotic therapy should be the standard of care for most patients with non-S. aureus BSI.

8/ We applied inverse probability of weighting (IPW) and instrumental variable (IV) approaches to account for the potential bias introduced by non-adherence. All analyses favored the 14-day group, and met the 4% NI margin for a conclusion of non-inferiority consistent with primary BALANCE results.

7/ Meanwhile, vascular catheter source and presence of antimicrobial resistance were associated with higher odds of treatment shortening in the 14-day arm. This latter finding was surprising; and may be due to the lack of available oral treatment options and preference to limit broad-spectrum abx.

6/ Patients receiving protocol-adherent treatment durations were significantly different from those who received non-adherent durations; multivariable models showed that higher disease severity, persistent fever/bacteremia, and lower age <70y were associated with higher odds of prolonged treatment.

5/ This histogram shows the wide spread of actual antibiotic durations received in both treatment arms, and illustrates the clear pattern of treatment crossover between arms. Median duration was 8 days (IQR 7-11) in the 7-day arm and 14 days (IQR 14-15) in the 14-day arm.

4/ In the BALANCE trial, 432/1802 (24%) of patients in the 7-day arm and 296/1779 (16.6%) of patients in the 14-day arm received treatment durations that were protocol non-adherent (>2 days longer or shorter than the assigned treatment duration).

3/ However, intention-to-treat and per-protocol approaches are both not ideal and do not adequately address this bias. There is no good consensus in guidelines or reporting standards on how best to address this non-adherence; though a variety of statistical techniques have been described.

2/ Non-adherence, especially with the treatment crossover pattern, is a threat to internal validity in non-inferiority trials, since it biases results towards no difference between groups, increasing the probability of a false conclusion of non-inferiority.

Hot off the press at @thelancetinfdis.bsky.social: our paper diving into non-adherence in the BALANCE trial. We identify factors associated with protocol non-adherence, and evaluate the impact of potential bias on trial results.

authors.elsevier.com/a/1m5He5E-Uo...

@steventong.bsky.social #IDSky

I can't say enough how incredible my experience with this joint PhD program has been. The coursework at @ihpmeuoft.bsky.social is truly world-class, and this is also a great opportunity to work with some amazing clinical trialists and build an international collaborative network.

We are looking for candidates for a new fully-funded joint PhD position at the Universities of Toronto and Melbourne, working on RCTs in bloodstream infection (BALANCE+, SNAP, STRAP).

More info here: forms.gle/H9TXEMkwM1cb...

Please spread far and wide!
@steventong.bsky.social #IDSky

I owe a lot to the site formerly known as Twitter (it's where I found my amazing joint PhD position thanks to a fortuitous post by @steventong.bsky.social), but it's completely unusable now and full of irrelevant material that I don't want to see. I no longer use it, and am firmly Team BlueSky!