In this situation, the correct course of action is to request the DSMB to conduct a thorough risk assessment and provide recommendations on unblinding the affected sub-group.

Reasoning:

The trial protocol specifies that unblinding should only occur if a life-threatening situation arises. Since the observed hepatotoxicity, although severe, does not automatically qualify as life-threatening, it is prudent to proceed cautiously.

Immediate unblinding of the entire trial (Option A) would compromise the study's integrity and could introduce bias.

Submitting the DSMB findings to the IRB/IEC (Option B) without first conducting a more thorough risk assessment may delay necessary safety measures.

Conducting a protocol amendment (Option C) without a comprehensive risk assessment may be premature.

Role of the DSMB:

The DSMB is responsible for evaluating safety data and making independent recommendations to protect trial participants. In this case, the DSMB should analyze the risk/benefit ratio of continuing the trial with the current protocol versus implementing safety modifications.

Ethical Considerations:

Protecting patient safety is paramount, but any unblinding must be justified by a clear and imminent risk. The DSMB's independent judgment is critical to making this decision without sponsor influence.

Verified Answer from Official Source:

According to GCP guidelines, any decision to unblind a study must be based on a comprehensive safety assessment, and the DSMB plays a key role in making unbiased recommendations regarding unblinding.

Exact Extract:

"Unblinding in a clinical trial should only occur when justified by critical safety concerns, as recommended by an independent data monitoring committee."

Objectives:

Maintain trial integrity while safeguarding patient safety.

Follow protocol and regulatory requirements for unblinding.

Ensure independent decision-making by the DSMB to avoid sponsor bias.