Adarsh Daswani, M.D.
4 extracted findings · 1 model-assigned issue type
FDA source excerpt, selected passage
From Study Day 1 until end of treatment, the protocol required subjects randomized (b)(4). You failed to adhere to these requirements. Specifically, (b)(4) doses were not administered to the following subjects randomized to receive (b)(4) and on (b)(4): i. For Subject (b)(6), thirty-four (b)(4) doses were not…
Findings and supporting evidence
Model-assisted readings, not an exhaustive interpretation. Compare with the extracted source findings below.
Failed to administer protocol-required doses to subjects randomized to (b)(4), including consecutive missed doses.
Supporting FDA text
Source excerpt · automated text-match checkFrom Study Day 1 until end of treatment, the protocol required subjects randomized (b)(4). You failed to adhere to these requirements. Specifically, (b)(4) doses were not administered to the following subjects randomized to receive (b)(4) and on (b)(4): i. For Subject (b)(6), thirty-four (b)(4) doses were not administered, including fourteen consecutive doses. ii. For Subject (b)(6), forty-three (b)(4) doses were not administered, including twelve consecutive doses from (b)(6). On (b)(6), this subject had severe (b)(4) and was hospitalized to receive 1 unit of packed red blood cells. iii. For Subject (b)(6), fifteen (b)(4) doses were not administered.
Failed to follow protocol-specified procedures for HemoCue Hgb ≥12 g/dL, including holding or reducing dose.
Supporting FDA text
Source excerpt · automated text-match checkThe protocol required that, if HemoCue Hgb was ≥12 g/dL at a study visit, HemoCue Hgb was to be repeated at the same study visit and the values were to be averaged. If HemoCue Hgb was repeated and confirmed to be ≥12 g/dL, randomized treatment dose was to be temporarily held. HemoCue Hgb was to be checked at a study visit 4 weeks later. If HemoCue Hgb was <11.5 g/dL, provided it had been at least 2 weeks since the previous study visit, randomized treatment was to be restarted at one dose step lower. You failed to adhere to these requirements. Specifically, Subject (b)(6), randomized to (b)(4), had a HemoCue Hgb of 12.6 g/dL, which was repeated and confirmed to be ≥12 g/dL (12.6 g/dL) on (b)(6). However, randomized treatment dose was not held, and (b)(4) was administered on (b)(6). Subsequently, on (b)(6), HemoCue Hgb was 12.7 g/dL, which was repeated and confirmed to be ≥12 g/dL (12.7 g/dL), and (b)(4) was held. However, on (b)(6), (b)(4) was administered, rather than reducing or holding the (b)(4) dose as required by the protocol. On (b)(6), HemoCue Hgb was <11.5 g/dL (10.9 g/dL). However, (b)(4) was not administered as required by the protocol, even though it had been at least 2 weeks since the previous study visit. Subsequently, on (b)(6), (b)(4) was administered without reducing the dose of (b)(4) by one dose step.
Findings extracted from the letter
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Source passage selected by the model
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What FDA requested
Model-assisted summary. Consult the letter for complete requests and conditions.
- Specify corrective actions you, as a clinical investigator, have taken or plan to take to prevent similar violations in the future, including details about policies to ensure compliance with the protocol, particularly regarding IRT transactions and treatment requirements.
Sections and clauses cited
As cited in this historical letter, not a statement of current regulatory requirements.