An independent research group evaluates a novel oral disease-modifying therapy compared to… — USMLE Step 3

An independent research group evaluates a novel oral disease-modifying therapy compared to conventional intravenous therapy for a rare autoimmune polyneuropathy. The primary efficacy endpoint is the prevention of permanent motor disability at 5 years. The primary safety endpoint is the incidence of drug-induced hepatotoxicity.

A retrospective cohort analysis of $5,000$ patients yields the following 5-year data:
- Novel therapy group ( $n = 2,000$ ): $140$ patients developed permanent motor disability, and $90$ patients developed hepatotoxicity.
- Conventional therapy group ( $n = 3,000$ ): $300$ patients developed permanent motor disability, and $60$ patients developed hepatotoxicity.

Assuming the differences in outcomes between the two groups are statistically significant, which of the following is the most accurate interpretation of the clinical impact of the novel therapy compared to the conventional therapy?

A
Treating $33$ patients will prevent one case of permanent motor disability, while treating $40$ patients will cause one additional case of hepatotoxicity.
B
Treating $4$ patients will prevent one case of permanent motor disability, while treating $40$ patients will cause one additional case of hepatotoxicity.
Treating $34$ patients will prevent one case of permanent motor disability, while treating $40$ patients will cause one additional case of hepatotoxicity.Cevap
D
Treating $34$ patients will prevent one case of permanent motor disability, while treating $67$ patients will cause one additional case of hepatotoxicity.
E
Treating $13$ patients will prevent one case of permanent motor disability, while treating $67$ patients will cause one additional case of hepatotoxicity.

Cevap

Treating 34 patients will prevent one case of permanent motor disability, while treating 40 patients will cause one additional case of hepatotoxicity.

The correct answer accurately calculates both the NNT and NNH using the absolute risk differences derived from the unequal cohort sizes. First, the incidence of disability is

7\%

(

140/2000

) for the novel therapy and

10\%

(

300/3000

) for conventional, yielding an Absolute Risk Reduction (ARR) of

3\%

(

0.03

). The NNT is

1/0.03 = 33.33

, which must be rounded UP to

34

to guarantee one prevented event. Second, the incidence of hepatotoxicity is

4.5\%

(

90/2000

) for the novel therapy and

2\%

(

60/3000

) for conventional, yielding an Absolute Risk Increase (ARI) of

2.5\%

(

0.025

). The NNH is

1/0.025 = 40

exact patients.

Adım Adım Çözüm

Calculate the absolute risk (incidence) of permanent motor disability for both groups.

Novel therapy risk =

\frac{140}{2000} = 0.07

(

7\%

). Conventional therapy risk =

\frac{300}{3000} = 0.10

(

10\%

Risk must be normalized to the group size before comparing outcomes, especially when cohort sizes are unequal.

Calculate the Absolute Risk Reduction (ARR) and the Number Needed to Treat (NNT) for disability.

ARR =

0.10 - 0.07 = 0.03

(

3\%

). NNT =

\frac{1}{0.03} = 33.33

ARR represents the absolute difference in favorable outcomes. NNT is the inverse of ARR.

Apply the appropriate rounding rule for NNT.

NNT rounds UP to

34

NNT must always be rounded up to the next whole integer to mathematically guarantee the prevention of at least one adverse event.

Calculate the absolute risk (incidence) of hepatotoxicity for both groups.

Novel therapy risk =

\frac{90}{2000} = 0.045

(

4.5\%

). Conventional therapy risk =

\frac{60}{3000} = 0.02

(

2\%

Safety endpoints must also be converted to incidence rates before absolute differences can be derived.

Calculate the Absolute Risk Increase (ARI) and Number Needed to Harm (NNH) for hepatotoxicity.

ARI =

0.045 - 0.02 = 0.025

(

2.5\%

). NNH =

\frac{1}{0.025} = 40

ARI measures the excess risk of an adverse event caused by the intervention. NNH is the inverse of ARI. Since it is an integer, no rounding is needed.

Anahtar Kavram

Calculation and interpretation of Absolute Risk Reduction (ARR), Absolute Risk Increase (ARI), Number Needed to Treat (NNT), and Number Needed to Harm (NNH) from raw cohort data with unequal group sizes.

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