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  "documentTitle": "Harmony Biosciences (HRMY)",
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  "notes": "The slide highlights a recurring methodological inconsistency across multiple clinical trials, suggesting regulatory oversight failure.",
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      "kind": "callout",
      "text": "Harmony 1 (top) and CTP (bottom) both use unexplained “centre effect” to adjust the endpoint values",
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      "text": "Footnote 7 in HARMONY CTP mentions HARMONY 1 as the inspiration for the “centres” reallocation, also used in HARMONY 1-bis",
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      "text": "“centres reallocation” to kick the trial over the finish line, leading both the EMA and FDA to cry foul despite Bioprojet’s attempt to portray it as pre-planned. HARMONY CTP used the same gimmick, which both agencies missed – a buried footnote states the",
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      "text": "Impenetrable phrases and assumptions are flung with abandon, a black box of statistical jargon and sorcery devoid of details necessary to comprehend or check the calculations. A recurring trick in the trials is what they call “small centres reallocation,”",
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      "text": "a mysterious post-hoc (after-the-fact) “adjustment” that takes endpoint data by trial site and tosses it into a martini shaker until the desired output spills out. The HARMONY I-bis study was a failure, as we shortly explain, where they tried a post-hoc",
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      "text": "“centre effect” was “suggested” by HARMONY 1, which also employs the same adjustment and was again missed by the FDA – which is significant given their reaction to it in HARMONY 1-bis.",
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      "text": "We adjusted final ESS for baseline values for assessment of the primary endpoint using a mixed linear analysis of covariance, assuming absence of treatment-baseline interaction term and accounting for random centre heterogeneity. Baseline ESS was the exposure at fixed dose); the primary efficacy outcome is cataplexy reduction identified as the rate ratio (pitolisant WCRfb/placebo WCRfb) between basal and final periods; the 1-month stable medication period is considered for final outcome assessment; and a centre effect, suggested by a previous study7 is taken into account. All the",
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      "text": "Footnote 7 in HARMONY CTP mentions HARMONY 1 as the inspiration for the “centres” reallocation, also used in HARMONY 1-bis — Scorpion Capital",
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      "text": "7 Dauvilliers Y, Bassetti C, Lammers GJ, et al. Pitolisant versus placebo or modafinil in patients with narcolepsy: a double-blind, randomised trial. Lancet Neurol 2013; 12: 1068–75.",
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      "text": "Source: https://pubmed.ncbi.nlm.nih.gov/24107292/; https://clinicaltrials.gov/ct2/history/NCT01067222?A=1&B=4&C=merged#StudyPageTop",
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      "kind": "title",
      "text": "Statistical tricks and gimmicks are a defining feature of each Bioprojet/Harmony clinical trial.",
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