In a 2x2 table comparing a rare adverse event between two drugs, several cells have expected frequencies less than 5. Which is the most appropriate test?

• A Standard Pearson chi-square test
• B McNemar's test
• C Student's t-test
• D Fisher's exact test ✓

Explanation

The chi-square approximation becomes unreliable when any expected cell frequency falls below 5 in a 2x2 table, and Fisher's exact test calculates the exact probability from the hypergeometric distribution without relying on large-sample assumptions. Student's t-test compares continuous means and McNemar's test applies to matched pairs, so neither addresses this design. Applying plain Pearson chi-square here would give a spuriously small p-value because its sampling distribution would not be approximated well.

Reference: Park's Textbook of Preventive and Social Medicine, 27th ed.

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