Dr. Anis Rassi Jr. MD, PhD on the challenges with the CHAGASICS trial.

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Controversies

Challenging the CHAGASICS Trial

Exposing the failures of peer review, Dr. Anis Rassi Jr. MD, PhD, recently published his letter to JAMA Cardiology in Sensible Medicine about glaring issues with the CHAGASICS trial.

• Dr. Rassi was one of the primary authors and designers of CHAGASICS, but resigned his authorship prior to publishing due to concerns about the study.
• CHAGASICS aimed to uncover if ICDs were more effective than amiodarone therapy for Chagas cardiomyopathy, finding that ICDs did show some benefits but didn’t reduce all-cause mortality.

The story began with Dr. Rassi expressing his concerns to the study’s editor at JAMA who advised him to submit a formal letter to JAMA’s Editor-in-Chief – which was ultimately rejected by the journal.

Outlining a list of issues with the study, Dr. Rassi’s letter focused on CHAGASICS’ design and reporting errors — and the trial’s design issues were glaring…

• The study was severely underpowered, only analyzing 323 patients (46% power) despite intending to enroll 1,100 (90% power).
• CHAGASICS also didn’t stick to its planned intention-to-treat analysis (ITT) and changed to a “modified ITT,” excluding 39 more patients from the already underpowered study.

Even more concerning than the design issues, the study’s authors made several major calculation and reporting mistakes…

• Medication usage was calculated based on the patient total (323) rather than the appropriate group sizes (157 for ICD, 166 for amiodarone), leading to massively incorrect medication usage rates (e.g. 38.1% in ICD group, when it should have been 78.3%).
• CHAGASICS reported a decrease in hospitalizations for the ICD group at three years, while reporting an increase in HF deaths in the same group over six years (which is “clinically nonsensical”).
• When it came to reporting ICD adverse events, the study’s authors reported 81 total ICD shocks despite only 48 appropriate shocks and 19 inappropriate shocks occurring (which adds up to 67).

Worst of all, no information about amiodarone use in the ICD group was included in the study, yet several ICD patients also received amiodarone, which casts doubt on the benefits that ICD patients experienced.

The Takeaway

While the significant issues with CHAGASICS’ design and reporting undermine its results, the bigger issue is the quality of scientific conduct that led to the study’s publication. How these mistakes made it past peer-review and the study’s editors has yet to be explained.

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The Wire

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The Resource Wire

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The Industry Wire

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8. GW Hospital residents avoid strike with last-minute deal.
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