A 57-year-old man presents to his oncologist to discuss management of small cell lung cancer. The patient is a lifelong smoker and was diagnosed with cancer 1 week ago. The patient states that the cancer was his fault for smoking and that there is "no hope now." He seems disinterested in discussing the treatment options and making a plan for treatment and followup. The patient says "he does not want any treatment" for his condition. Which of the following is the most appropriate response from the physician?

"It must be very challenging having received this diagnosis. I want to work with you to create a plan."

"You seem upset at the news of this diagnosis. I want you to go home and discuss this with your loved ones and come back when you feel ready to make a plan together for your care."

"It must be tough having received this diagnosis; however, new cancer therapies show increased efficacy and excellent outcomes."

"We are going to need to treat your lung cancer. I am here to help you throughout the process."

"I respect your decision and we will not administer any treatment. Let me know if I can help in any way."

In 2006, three researchers from North Carolina wanted to examine the benefits of treating the risk of suicidality in children and adolescents by looking at randomized, multicenter, controlled trials of sertraline usage compared to placebo. Their analysis found clinically significant benefits of the drug and a positive benefit-to-risk ratio for sertraline in adolescents with major depressive disorder. They also found that 64 depressed children and adolescents need to receive the drug for 1 extra patient to experience suicidality as an adverse outcome. In other words, if 64 treated individuals received sertraline, some would experience suicidality due to their illness, some would not experience suicidality, and 1 individual would become suicidal due to the unique contribution of sertraline. Which of the following statements is true for this measure (defined as the inverse of the attributable risk), which aims to describe adverse outcomes this way?

Input values must be probabilities of the events of interest.

Higher measures indicate greater risk.

Multiple risks can be contained and described within one result.

The final metric represents proportions in percentage terms.

The measure can include multiple events at one time.

A 28-year-old male presents to his primary care physician with complaints of intermittent abdominal pain and alternating bouts of constipation and diarrhea. His medical chart is not significant for any past medical problems or prior surgeries. He is not prescribed any current medications. Which of the following questions would be the most useful next question in eliciting further history from this patient?

"Can you tell me more about the symptoms you have been experiencing?"

"Does the diarrhea typically precede the constipation, or vice-versa?"

"Is the diarrhea foul-smelling?"

"Please rate your abdominal pain on a scale of 1-10, with 10 being the worst pain of your life"

"Are the symptoms worse in the morning or at night?"

A pharmaceutical company reports a new antihypertensive drug reduces cardiovascular events with an NNT of 50 over 5 years based on a trial of 10,000 patients. An independent analysis reveals the benefit was driven entirely by a subgroup with resistant hypertension (20% of participants, NNT=15), while the remaining 80% showed no benefit over standard therapy (NNT approaching infinity). Evaluate the ethical and regulatory implications of reporting the overall NNT.

The overall NNT is misleading; approval should be restricted to resistant hypertension population where benefit is demonstrated

Conduct a new trial in the general hypertensive population to validate efficacy before broader approval

The subgroup analysis represents data dredging; only the overall NNT should be used for clinical decisions

The overall NNT of 50 is statistically valid and appropriate for regulatory approval and marketing

Report both overall and subgroup NNTs; allow clinicians to determine appropriate use based on patient characteristics

Limitations and common misinterpretations

Limitations - NNT's Shaky Foundation

Highly Dependent on Baseline Risk: NNT is the reciprocal of Absolute Risk Reduction ($1/ARR$). It is not a fixed property of a drug. A low baseline risk in a population inflates the NNT, making an effective therapy seem less useful.
No Sense of Scale: NNT doesn't differentiate between preventing minor outcomes (e.g., headache) and major ones (e.g., death). It only counts events avoided.
Time-Bound: An NNT is only valid for the specific duration of the study it came from. A 1-year NNT cannot be compared to a 5-year NNT.
Confidence Interval Issues: The 95% CI for an NNT can be very wide and may cross infinity, making precise interpretation difficult.

⭐ Always check the baseline risk of the study population! An NNT is meaningless without knowing the underlying risk of the event.

Misinterpretations - Comparing Apples & Oranges

Directly comparing NNTs across different studies or interventions is a common pitfall. This is often like comparing apples to oranges because NNT is highly context-dependent and sensitive to multiple variables.

Baseline Risk Differences: NNT is acutely sensitive to the baseline risk (Control Event Rate, CER).
- A study in a high-risk population (higher CER) will show a lower NNT than a study in a low-risk group, even if the relative risk reduction is identical.
Heterogeneity in Studies: Comparability is often invalid due to differences in:
- Populations: Age, severity of illness, comorbidities.
- Interventions: Drug dosage, duration of treatment, co-therapies.
- Outcomes: Varying definitions of what constitutes an "event".

⭐ Pearl: NNT is an absolute, not relative, measure. Therefore, always inspect the study's baseline risk (CER) before applying an NNT to your patient population. An NNT from a tertiary care center trial may not apply to a primary care setting.

Misinterpretations - Not a Crystal Ball

Group Average, Not Individual Forecast: NNT applies to a population, not a single patient. An NNT of 10 implies that for every 10 patients treated, one additional person benefits on average.
A Game of Odds, Not Certainty: Treatment provides a probability of benefit (the ARR). The NNT ($1/ARR$) is just another way to express this probability. Every patient gets the same improved odds.
Context-Dependent: NNT values are tied to a specific study's population and timeframe. They may not be generalizable to patients with different baseline risks.
Frequency, Not Magnitude: NNT indicates how many people are affected, but not the size or importance of the effect (e.g., preventing a mild rash vs. preventing a fatal MI).

⭐ An NNT is meaningless without its time component. An NNT of 25 to prevent one death over 1 year is vastly different from an NNT of 25 over 10 years.

NNT is highly dependent on baseline risk and is not a constant biological value.

It oversimplifies outcomes to a binary event, ignoring the spectrum of disease severity.

NNT values do not specify the timeframe over which the benefit or harm occurs.

Comparing NNTs across studies is often invalid due to different patient populations and methodologies.

A large NNT can still be clinically important for preventing rare but catastrophic events.