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Evidence-based GLP-1 & peptide discussion since 2023
ForumsPublic SquareI just want to eat pizza again is that too much to ask — what worked for you?

I just want to eat pizza again is that too much to ask — what worked for you?

TrialNerd_Beth Tue, Sep 24, 2024 at 11:35 AM 11 replies 1,831 viewsPage 1 of 3
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TrialNerd_Beth
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Bethesda, MD
Sep 24, 2024 at 11:35 AM#1

My own curve sits about four points below the published mean and I spent two months assuming that meant something was wrong with me or with my material.

A quick sanity check on any figure quoted here: is it mean or median, is it intention-to-treat or completers, and what was the comparator. Three questions, and they resolve most disagreements in these threads.

What I am trying to establish is how to read a result like this without either dismissing it or over-reading it, since the summaries all read like press releases.

Tell me what I have not thought of.

6 9RickReta_CO, PharmHunterJen, TomTeleRx and 3 others
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LarryQC_SD
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Sep 24, 2024 at 11:51 AM#2

Taking the question as asked, rather than the general version of it. Read four things before the headline number. The population, because trial populations are selected and supported in ways that real cohorts are not. The comparator, because "better than placebo" and "better than the current standard" are different claims and get reported identically. The primary endpoint as pre-registered, because a secondary endpoint promoted after the fact is a hypothesis rather than a finding. And the completion rate, because a large effect in the half of participants who finished is a different result from a large effect in everybody enrolled.

I would rather be corrected than agreed with, if it comes to it.

7 10paul_denver, TinaHashiRN, robert_kc and 4 others
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sarah_nash92
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Nashville, TN
Sep 24, 2024 at 12:07 PM#3
LarryQC_SD said:
Read four things before the headline number.

Forest plot interpretation for the the trial evidence meta-analysis: when reading the pooled estimate, pay attention to:

  1. Point estimate (HR/RR/OR) — center of the diamond
  2. Confidence interval width — precision of the estimate
  3. I² statistic — heterogeneity across studies
  4. Individual study weights — are results driven by one large trial?
  5. Prediction interval — range of plausible true effects in future settings

The the trial evidence meta-analysis shows a pooled RR of 0.72 (95% CI 0.67-0.82), I²=30%. This is a robust and consistent effect.

8 11ZaraB_AL, JakeSmashed95, NauseaFreeNow and 5 others
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DeniseRN_TPA
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Sep 24, 2024 at 12:23 PM#4
TrialNerd_Beth said:
My own curve sits about four points below the published mean and I spent two months assuming that meant something was wrong with me or with my…

This matches mine closely enough to be worth saying so. Relative and absolute effects need reading together. A 20% relative reduction on a high baseline risk is a large absolute benefit; the same relative figure on a low baseline risk is a small one, and press summaries almost always quote the relative number because it is bigger.

9 12LindaRN_retired, tommy_boulder, hyun_seoul and 6 others
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lisa_labSD
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Oct 2024
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Sep 24, 2024 at 1:46 PM#5

Adding the clinical framing, because it changes how the question reads.

Bayesian meta-analysis perspective on the trial evidence: traditional frequentist meta-analyses report point estimates and confidence intervals. Bayesian approaches provide probability distributions that are more intuitive for clinical decision-making.

For example: "There is a 98.5% probability that semaglutide 2.4mg produces >10% weight loss vs placebo" is more actionable than "RR 3.4, 95% CI 2.8-4.1, p<0.001."

The the trial evidence evidence is strong under both frameworks, but Bayesian analysis better communicates the degree of certainty for individual patient counseling.

10 13cory_ATX, lori_vegas, Dr.PulmRoch and 7 others
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