An ongoing dialogue on HIV/AIDS, infectious diseases,
September 23rd, 2018
Picking Your Next ID Journal Club Paper? MERINO or POET Trial? Two ID Fellows Debate
Late afternoon/early evening at an academic medical center. Bright young doctors sit in a hospital workroom, putting the finishing touches on what are undoubtedly the most comprehensive and, yes, simply the best consult notes in their respective patient’s electronic medical records.
Best ever.
ID Fellow #1: Hey, pretty soon we have to do Journal Club, right?
ID Fellow #2: Yep, coming up. And you’re first! And I’m the following week. Most important question — do they feed us at these conferences?
ID Fellow #1: Not sure — this is one of the hardest things about fellowship. You never can tell when there’s food. During residency, there was always food.
ID Fellow #2: Agree, big drop off. That food issue and late afternoon consults might be the hardest thing about this year.
A bit more work is done on their respective masterpieces — one a 2000-word opus summarizing a 6-week hospitalization involving several surgeries and a prolonged ICU stay, the other a 9-year history of recurrent lower extremity ulcers in a diabetic with vascular disease.
ID Fellow #1: I think I’m going to choose the MERINO trial — piperacillin-tazobactam [he didn’t really say “piperacillin-tazobactam,” but used the Z-word, alas] vs. meropenem in ceftriaxone-resistant [mostly ESBL] bacteremia. Mero was better! Great to have a definitive result.
ID Fellow #2 (somewhat warily, since obviously she was going to pick the same paper): Yes, meropenem was better, but not superior — in other words, pip-tazo was not demonstrated to be noninferior to mero in the primary endpoint, which was all-cause mortality at 30 days after randomization. (Sensing weakness.) You sure you have the statistical chops to discuss this?
ID Fellow #1 (clearly wavering): Erm … not sure. So not noninferior? Yikes, that double negative is confusing. But it will give me a chance to review the purpose of noninferiority studies. I remember in my med school stats class, one of my favorite teachers said we should replace “noninferior” with “Not too much worse than …” Always liked that. You know, real English.
ID Fellow #2 (thinking that MERINO is now taken, so might as well be generous with her knowledge): Hey, if you really want to get down the statistical rabbit hole in MERINO, there’s a great review I read online about it — I can text you the link. Plus, the investigators amazingly did a really interesting thread on Twitter, answering some of the most common questions they’ve been getting. How great is it that?
ID Fellow #1 (sensing that he may be out of his league on MERINO): OK … maybe you should do MERINO. I was also thinking of the POET trial — IV vs. oral antibiotics for endocarditis. Oral was noninferior. Highly relevant, and I still get to show off by discussing noninferiority trials.
ID Fellow #2 (delighted that she now has MERINO back): Great choice! Could be “practice-changing”; always good to cover a study where you can bring out that powerful phrase. Plus, no gels or blots or GWAS to explain.
ID Fellow #1: Yep, it’s a great study. But I do have some issues. The eligible patients had to receive at least 10 days of IV therapy before randomization — why 10 days?
ID Fellow #2: Follows the rules.
ID Fellow #1: Amazingly, there was no MRSA! And only around 1% had injection drug use as a risk factor — both limit generalizability. Plus, the oral regimens are weird. Fusidic acid? What the [word unintelligible] is that? And putting the drugs used in the supplementary appendix was a bizarre decision, almost like they were trying to hide something. You can tell it was presented at a cardiology and not an ID meeting. We’d never tolerate that.
ID Fellow #2 (worried he might go back and take MERINO): So are you saying you don’t like the study?
ID Fellow #1: No, I think it’s great — imagine how many fewer vanco levels we’d need to chase if PO antibiotics became standard of care for endocarditis! It’s just not perfect. But it’s the exact sort of study we should see more often. It asks an important clinical question, and answers it.
ID Fellow #2: You mean like oral vs. IV antibiotics for osteomyelitis?
ID Fellow #1: Exactly! Hey, what happened to that study?
They go back to putting the finishing touches on their notes. The signed notes get transmitted electronically to an ID attending — who feels deep gratitude about working with such a smart and dedicated bunch, believe me.
“Non-inferior” is my least favorite word in study conclusions. Inevitably elicits an eyeroll from me, especially when some fancy new, expensive drug is being compared to an older, relatively-inexpensive, tried-and-true drug.
Very surprised that there were only 5 IV drug users in the POET trial. That definitely limits generalizability.
I often wonder how much time PIs and their staffs spend trying to come up with cute study names like MARINO and POET. Or does that sort of thing just come naturally to some people?
Perhaps it’s just my COI as author, but it seems to me that the POET authors gave remarkably short shrift to the OATE study (Heldman AW, et al, cited ref #15 https://www.ncbi.nlm.nih.gov/pubmed/8686718 ), which was a randomized controlled study of oral versus intravenous therapy in PWID who had right-sided MSSA endocarditis.
Well, in an historical epoch of chaos it’s nice to know that nothing has changed fundamentally in the ward room since 1982. Thanks for this old man.
Nice to see some conversations in fellowship are universal. I will be curious to see what everyone thinks of the POET study at your journal club. Our group was quite concerned about the lack of any information on what IV antibiotics were given to the control arm (and for how long) and the choice of PO regimens – the supplemental tables show that one patient was actually prescribed PO vancomycin for their endocarditis (no instances of c. diff reported in the paper that would account for this).
That’s an old stamp – it’s a long time since it cost 3p to post anything in the UK!
But very appropriate, sadly, for an ID thread.
Fellow #2 is a prik.