Number needed to treat/harm

Number needed to treat/harm US Medical PG Question 1: A research team develops a new monoclonal antibody checkpoint inhibitor for advanced melanoma that has shown promise in animal studies as well as high efficacy and low toxicity in early phase human clinical trials. The research team would now like to compare this drug to existing standard of care immunotherapy for advanced melanoma. The research team decides to conduct a non-randomized study where the novel drug will be offered to patients who are deemed to be at risk for toxicity with the current standard of care immunotherapy, while patients without such risk factors will receive the standard treatment. Which of the following best describes the level of evidence that this study can offer?

• A. Level 1
• B. Level 3 (Correct Answer)
• C. Level 5
• D. Level 4
• E. Level 2

Number needed to treat/harm Explanation: ***Level 3*** - A **non-randomized controlled trial** like the one described, where patient assignment to treatment groups is based on specific characteristics (risk of toxicity), falls into Level 3 evidence. - This level typically includes **non-randomized controlled trials** and **well-designed cohort studies** with comparison groups, which are prone to selection bias and confounding. - The study compares two treatments but lacks randomization, making it Level 3 evidence. *Level 1* - Level 1 evidence is the **highest level of evidence**, derived from **systematic reviews and meta-analyses** of multiple well-designed randomized controlled trials or large, high-quality randomized controlled trials. - The described study is explicitly stated as non-randomized, ruling out Level 1. *Level 2* - Level 2 evidence involves at least one **well-designed randomized controlled trial** (RCT) or **systematic reviews** of randomized trials. - The current study is *non-randomized*, which means it cannot be classified as Level 2 evidence, as randomization is a key criterion for this level. *Level 4* - Level 4 evidence includes **case series**, **case-control studies**, and **poorly designed cohort or case-control studies**. - While the study is non-randomized, it is a controlled comparative trial rather than a case series or retrospective case-control study, placing it at Level 3. *Level 5* - Level 5 evidence is the **lowest level of evidence**, typically consisting of **expert opinion** without explicit critical appraisal, or based on physiology, bench research, or animal studies. - While the drug was initially tested in animal studies, the current human comparative study offers a higher level of evidence than expert opinion or preclinical data.

Number needed to treat/harm US Medical PG Question 2: A 33-year-old man is brought by ambulance to the emergency room after being a passenger in a motor vehicle accident. An empty bottle of whiskey was found in his front seat, and the patient admits to having been drinking all night. He has multiple lacerations and bruising on his face and scalp and a supportive cervical collar is placed. He is endorsing a significant headache and starts vomiting in the emergency room. His vitals, however, are stable, and he is transported to the CT scanner. While there, he states that he does not want to have a CT scan and asks to be released. What is the most appropriate course of action?

• A. Have the patient fill the appropriate forms and discharge against medical advice
• B. Explain to him that he is intoxicated and cannot make health care decisions, continue as planned (Correct Answer)
• C. Release the patient as requested
• D. Agree to not do the CT scan
• E. Call security

Number needed to treat/harm Explanation: ***Explain to him that he is intoxicated and cannot make health care decisions, continue as planned*** - The patient's **intoxication** (empty whiskey bottle, admitted drinking all night) and **head injury symptoms** (headache, vomiting after MVA) suggest he lacks the capacity to make informed medical decisions. - When a patient lacks capacity, the medical team has an ethical and legal obligation to act in their **best interest**, which includes performing necessary diagnostic tests like a CT scan to rule out serious intracranial injuries. *Have the patient fill the appropriate forms and discharge against medical advice* - Discharging a patient against medical advice requires they have the **full capacity** to understand the risks and benefits of their decision, which is compromised by intoxication and head trauma. - Doing so without ensuring capacity places the patient at significant risk and could have **legal implications** for the healthcare provider and institution. *Release the patient as requested* - Releasing an intoxicated patient with a potential **head injury** into the community is medically negligent and highly dangerous given the risk of worsening neurological status. - Such an action disregards the principle of **beneficence** and the duty to prevent harm, especially when capacity is in question. *Agree to not do the CT scan* - Refusing a necessary diagnostic test like a **CT scan** for a patient with head trauma and altered mental status (due to intoxication) can lead to missed diagnoses of life-threatening conditions like intracranial hemorrhage. - This decision would allow the patient to leave without proper assessment, potentially jeopardizing their life and violating the standard of care to **stabilize** and **diagnose**. *Call security* - While security might be needed if the patient becomes disruptive or aggressive, simply calling security without attempting to explain the situation or assess capacity doesn't address the primary medical and ethical dilemma. - The immediate priority is to ensure the patient's well-being and assess their cognitive ability to make choices, with security being a secondary measure for **safety** if necessary.

Number needed to treat/harm US Medical PG Question 3: A 62-year-old man comes to the physician in May for a routine health maintenance examination. He feels well. He underwent a right inguinal hernia repair 6 months ago. He has hypertension and type 2 diabetes mellitus. There is no family history of serious illness. Current medications include metformin, sitagliptin, enalapril, and metoprolol. He received the zoster vaccine 1 year ago. He received the PPSV23 vaccine 4 years ago. His last colonoscopy was 7 years ago and was normal. He smoked a pack of cigarettes a day for 20 years but quit 17 years ago. He drinks two to three alcoholic beverages on weekends. He is allergic to amoxicillin. He is scheduled to visit Australia and New Zealand in 2 weeks to celebrate his 25th wedding anniversary. He appears healthy. Vital signs are within normal limits. An S4 is heard at the apex. The remainder of the examination shows no abnormalities. Which of the following is the most appropriate recommendation at this time?

• A. Colonoscopy
• B. Influenza vaccine (Correct Answer)
• C. Pneumococcal conjugate vaccine 13
• D. Cardiac stress test
• E. Abdominal ultrasound

Number needed to treat/harm Explanation: ***Influenza vaccine*** - Current guidelines recommend annual **influenza vaccination** for all adults, particularly those over 60 years old and those with chronic medical conditions like diabetes and hypertension. - **Critical timing consideration**: The patient is traveling to Australia and New Zealand (Southern Hemisphere) in 2 weeks, where it will be **winter season** (May-September) with peak influenza activity. - He is a **high-risk patient** (age >60, diabetes, hypertension, cardiovascular disease) who should receive influenza vaccine before travel to areas experiencing influenza season. - This is the **most appropriate and time-sensitive recommendation** at this visit. *Colonoscopy* - The patient had a normal colonoscopy 7 years ago; current guidelines suggest a repeat colonoscopy every **10 years** for average-risk individuals. - There are no new symptoms, family history, or risk factors that would necessitate an earlier repeat colonoscopy at this time. *Pneumococcal conjugate vaccine 13* - The patient received **PPSV23** four years ago at approximately age 58. - Per **current CDC guidelines (2019+)**, PCV13 is **no longer routinely recommended** for immunocompetent adults ≥65 years old. - PPSV23 alone is now the standard recommendation for adults ≥65, which this patient has already received. - PCV13 may be considered through **shared decision-making** in specific circumstances, but is not a routine or urgent recommendation. *Cardiac stress test* - Although the patient has risk factors for cardiovascular disease (hypertension, diabetes, former smoker) and an **S4 heart sound** (indicating **left ventricular hypertrophy**), he is asymptomatic. - Routine **screening stress tests** are not recommended for asymptomatic individuals without signs of active cardiac ischemia. *Abdominal ultrasound* - There are **no symptoms** or specific indications (e.g., abdominal aortic aneurysm screening criteria not met - would need age 65-75 with smoking history). - The patient is 62 years old and quit smoking 17 years ago, so AAA screening criteria are not yet met. - Routine screening abdominal ultrasounds are not indicated.

Number needed to treat/harm US Medical PG Question 4: A research team is studying the effects of a novel drug that was discovered to treat type 2 diabetes. In order to learn more about its effects, they follow patients who are currently taking the drug and determine whether there are adverse effects that exceed anticipated levels and may therefore be drug-related. They discover that the drug causes an excess of sudden cardiac death in 19 patients with renal failure out of 2 million total patients that are followed. Based on these results, an additional warning about this serious adverse effect is added to the investigator brochure for the drug. Which of the following clinical phase studies does this study most likely describe?

• A. Phase IV (Correct Answer)
• B. Phase II
• C. Phase V
• D. Phase III
• E. Phase I

Number needed to treat/harm Explanation: ***Phase IV*** - This study occurs **after a drug has been approved and marketed**, focusing on post-marketing surveillance for long-term safety, effectiveness, and real-world side effects in a large and diverse patient population. - The discovery of a rare but serious adverse effect (sudden cardiac death) in a large patient population (2 million) after the drug is already in use is characteristic of a **Phase IV clinical trial**. *Phase II* - Phase II trials involve a **larger group of patients (hundreds)** and focus on evaluating the drug's effectiveness and further assessing safety in patients with the target condition. - This phase is typically conducted **before widespread marketing** and would not involve 2 million patients. *Phase V* - There is **no widely recognized "Phase V"** in standard clinical trial terminology (Phases I-IV focus on drug development and post-marketing surveillance). - This term is sometimes used informally to refer to **health economics and outcomes research** or implementation studies, which are not described in the scenario. *Phase III* - Phase III trials are large-scale studies involving **thousands of patients** to confirm effectiveness, monitor side effects, compare the drug to standard treatments, and collect information for safe use. - While large, these trials are conducted **before regulatory approval** and marketing, and would not typically follow 2 million patients already taking the drug in the real world. *Phase I* - Phase I trials are the **first stage of human testing**, involving a small group of healthy volunteers (20-100) to assess safety, dosage, and pharmacokinetics. - The primary goal is to determine if the drug is safe enough for further testing, not to identify rare adverse events in a large patient population.

Number needed to treat/harm US Medical PG Question 5: You are reading through a recent article that reports significant decreases in all-cause mortality for patients with malignant melanoma following treatment with a novel biological infusion. Which of the following choices refers to the probability that a study will find a statistically significant difference when one truly does exist?

• A. Type II error
• B. Type I error
• C. Confidence interval
• D. p-value
• E. Power (Correct Answer)

Number needed to treat/harm Explanation: ***Power*** - **Power** is the probability that a study will correctly reject the null hypothesis when it is, in fact, false (i.e., will find a statistically significant difference when one truly exists). - A study with high power minimizes the risk of a **Type II error** (failing to detect a real effect). *Type II error* - A **Type II error** (or **beta error**) occurs when a study fails to reject a false null hypothesis, meaning it concludes there is no significant difference when one actually exists. - This is the **opposite** of what the question describes, which asks for the probability of *finding* a difference. *Type I error* - A **Type I error** (or **alpha error**) occurs when a study incorrectly rejects a true null hypothesis, concluding there is a significant difference when one does not actually exist. - This relates to the **p-value** and the level of statistical significance (e.g., p < 0.05). *Confidence interval* - A **confidence interval** provides a range of values within which the true population parameter is likely to lie with a certain degree of confidence (e.g., 95%). - It does not directly represent the probability of finding a statistically significant difference when one truly exists. *p-value* - The **p-value** is the probability of observing data as extreme as, or more extreme than, that obtained in the study, assuming the null hypothesis is true. - It is used to determine statistical significance, but it is not the probability of detecting a true effect.

Number needed to treat/harm US Medical PG Question 6: 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?

• A. "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."
• B. "It must be tough having received this diagnosis; however, new cancer therapies show increased efficacy and excellent outcomes."
• C. "It must be very challenging having received this diagnosis. I want to work with you to create a plan." (Correct Answer)
• D. "We are going to need to treat your lung cancer. I am here to help you throughout the process."
• E. "I respect your decision and we will not administer any treatment. Let me know if I can help in any way."

Number needed to treat/harm Explanation: ***"It must be very challenging having received this diagnosis. I want to work with you to create a plan."*** - This response **acknowledges the patient's emotional distress** and feelings of guilt and hopelessness, which is crucial for building rapport and trust. - It also gently **re-engages the patient** by offering a collaborative approach to treatment, demonstrating the physician's commitment to supporting him through the process. *"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."* - While acknowledging distress, sending the patient home without further engagement **delays urgent care** for small cell lung cancer, which is aggressive. - This response might be perceived as dismissive of his immediate feelings and can **exacerbate his sense of hopelessness** and isolation. *"It must be tough having received this diagnosis; however, new cancer therapies show increased efficacy and excellent outcomes."* - This statement moves too quickly to treatment efficacy without adequately addressing the patient's current **emotional state and fatalism**. - While factual, it **lacks empathy** for his personal feelings of blame and hopelessness, potentially making him feel unheard. *"We are going to need to treat your lung cancer. I am here to help you throughout the process."* - This response is **too directive and authoritarian**, which can alienate a patient who is already feeling guilty and resistant to treatment. - It fails to acknowledge his stated feelings of "no hope now" or his disinterest in treatment, which are critical to address before discussing the necessity of treatment. *"I respect your decision and we will not administer any treatment. Let me know if I can help in any way."* - While respecting patient autonomy is vital, immediately accepting a patient's decision to refuse treatment without exploring the underlying reasons (e.g., guilt, hopelessness, lack of information) is **premature and potentially harmful**. - The physician has a responsibility to ensure the patient is making an informed decision, especially for a rapidly progressing condition like small cell lung cancer.

Number needed to treat/harm US Medical PG Question 7: A student health coordinator plans on leading a campus-wide HIV screening program that will be free for the entire undergraduate student body. The goal is to capture as many correct HIV diagnoses as possible with the fewest false positives. The coordinator consults with the hospital to see which tests are available to use for this program. Test A has a sensitivity of 0.92 and a specificity of 0.99. Test B has a sensitivity of 0.95 and a specificity of 0.96. Test C has a sensitivity of 0.98 and a specificity of 0.93. Which of the following testing schemes should the coordinator pursue?

• A. Test A on the entire student body followed by Test B on those who are positive
• B. Test A on the entire student body followed by Test C on those who are positive
• C. Test C on the entire student body followed by Test B on those who are positive
• D. Test C on the entire student body followed by Test A on those who are positive (Correct Answer)
• E. Test B on the entire student body followed by Test A on those who are positive

Number needed to treat/harm Explanation: ***Test C on the entire student body followed by Test A on those who are positive*** - To "capture as many correct HIV diagnoses as possible" (maximize true positives), the initial screening test should have the **highest sensitivity**. Test C has the highest sensitivity (0.98). - To "capture as few false positives as possible" (maximize true negatives and confirm diagnoses), the confirmatory test should have the **highest specificity**. Test A has the highest specificity (0.99). *Test A on the entire student body followed by Test B on those who are positive* - Starting with Test A (sensitivity 0.92) would miss more true positive cases than starting with Test C (sensitivity 0.98), failing the goal of **capturing as many cases as possible**. - Following with Test B (specificity 0.96) would result in more false positives than following with Test A (specificity 0.99). *Test A on the entire student body followed by Test C on those who are positive* - This scheme would miss many true positive cases initially due to Test A's lower sensitivity compared to Test C. - Following with Test C would introduce more false positives than necessary, as it has a lower specificity (0.93) than Test A (0.99). *Test C on the entire student body followed by Test B on those who are positive* - While Test C is a good initial screen for its high sensitivity, following it with Test B (specificity 0.96) is less optimal than Test A (specificity 0.99) for minimizing false positives in the confirmation step. - This combination would therefore yield more false positives in the confirmatory stage than using Test A. *Test B on the entire student body followed by Test A on those who are positive* - Test B has a sensitivity of 0.95, which is lower than Test C's sensitivity of 0.98, meaning it would miss more true positive cases at the initial screening stage. - While Test A provides excellent specificity for confirmation, the initial screening step is suboptimal for the goal of capturing as many diagnoses as possible.

Number needed to treat/harm US Medical PG Question 8: 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?

• A. Higher measures indicate greater risk.
• B. Input values must be probabilities of the events of interest. (Correct Answer)
• C. Multiple risks can be contained and described within one result.
• D. The final metric represents proportions in percentage terms.
• E. The measure can include multiple events at one time.

Number needed to treat/harm Explanation: ***Input values must be probabilities of the events of interest.*** - The measure described (- the inverse of the **attributable risk** - or more accurately, the **Number Needed to Harm** or **NNH**) is derived from **absolute risk reduction**, which requires the risk of an event in the exposed group and the risk of the event in the unexposed/control group to be expressed as **probabilities or proportions**. - These probabilities are essential for calculating the difference in event rates, which is then inverted to get the NNH. *Higher measures indicate greater risk.* - A **higher NNH** (e.g., 64 in this case) indicates that a larger number of patients need to be treated for one additional adverse event to occur, implying a **lower risk** associated with the treatment. - Conversely, a **lower NNH** (e.g., 10) would mean fewer patients need to be treated for one additional adverse event, indicating a **higher risk**. *Multiple risks can be contained and described within one result.* - The NNH (or Number Needed to Treat) is typically calculated for a **single specific outcome** (either beneficial or harmful). - While an overall benefit-to-risk analysis might involve considering multiple outcomes, the NNH itself quantifies the impact for **one defined event**. *The final metric represents proportions in percentage terms.* - The final metric (NNH) is expressed as a **whole number** (e.g., 64), representing the number of patients. - It does **not represent a proportion or a percentage**; rather, it indicates how many individuals need to be exposed to experience one additional event. *The measure can include multiple events at one time.* - The NNH is event-specific; it calculates the number of patients for **one particular adverse event**. - To analyze multiple events, one would need to calculate **separate NNH values** for each individual event.

Number needed to treat/harm US Medical PG Question 9: A survey was conducted in a US midwestern town in an effort to assess maternal mortality over the past year. The data from the survey are given in the table below: Women of childbearing age 250,000 Maternal deaths 2,500 Number of live births 100, 000 Number of deaths of women of childbearing age 7,500 Maternal death is defined as the death of a woman while pregnant or within 42 days of termination of pregnancy from any cause related to or aggravated by, the pregnancy. Which of the following is the maternal mortality rate in this midwestern town?

• A. 1,000 per 100,000 live births
• B. 33 per 100,000 live births
• C. 3,000 per 100,000 live births
• D. 33,300 per 100,000 live births
• E. 2,500 per 100,000 live births (Correct Answer)

Number needed to treat/harm Explanation: ***2,500 per 100,000 live births*** - The maternal mortality rate is calculated as the number of **maternal deaths** per 100,000 **live births**. The given data directly provide these values. - Calculation: (2,500 maternal deaths / 100,000 live births) × 100,000 = **2,500 per 100,000 live births**. *1,000 per 100,000 live births* - This value is incorrect as it does not align with the provided numbers for maternal deaths and live births in the calculation. - It might result from a miscalculation or using incorrect numerator/denominator values from the dataset. *33 per 100,000 live births* - This value is significantly lower than the correct rate and suggests a substantial error in calculation or an incorrect understanding of how the maternal mortality rate is derived. - It could potentially result from dividing the number of live births by maternal deaths, which is the inverse of the correct formula. *3,000 per 100,000 live births* - This option is close to the correct answer but slightly higher, indicating a possible calculation error, for instance, including non-maternal deaths or other causes of deaths in the numerator. - The definition of maternal death is specific to pregnancy-related or aggravated causes, so extraneous deaths would inflate the rate. *33,300 per 100,000 live births* - This figure results from incorrectly calculating the proportion of maternal deaths among all deaths of women of childbearing age: (2,500 / 7,500) × 100,000 = 33,333. - This is a conceptual error as the maternal mortality rate should use live births as the denominator, not total deaths of women of childbearing age.

Number needed to treat/harm US Medical PG Question 10: In a randomized controlled trial studying a new treatment, the primary endpoint (mortality) occurred in 14.4% of the treatment group and 16.7% of the control group. Which of the following represents the number of patients needed to treat to save one life, based on the primary endpoint?

• A. 1/(0.144 - 0.167)
• B. 1/(0.167 - 0.144) (Correct Answer)
• C. 1/(0.300 - 0.267)
• D. 1/(0.267 - 0.300)
• E. 1/(0.136 - 0.118)

Number needed to treat/harm Explanation: ***1/(0.167 - 0.144)*** - The **Number Needed to Treat (NNT)** is calculated as **1 / Absolute Risk Reduction (ARR)**. - The **Absolute Risk Reduction (ARR)** is the difference between the event rate in the control group (16.7%) and the event rate in the treatment group (14.4%), which is **0.167 - 0.144**. *1/(0.144 - 0.167)* - This calculation represents 1 divided by the **Absolute Risk Increase**, which would be relevant if the treatment increased mortality. - The **NNT should always be a positive value**, indicating the number of patients to treat to prevent one adverse event. *1/(0.300 - 0.267)* - This option uses arbitrary numbers (0.300 and 0.267) that do not correspond to the given **mortality rates** in the problem. - It does not reflect the correct calculation for **absolute risk reduction** based on the provided data. *1/(0.267 - 0.300)* - This option also uses arbitrary numbers not derived from the problem's data, and it would result in a **negative value** for the denominator. - The difference between event rates of 0.267 and 0.300 is not present in the given information for this study. *1/(0.136 - 0.118)* - This calculation uses arbitrary numbers (0.136 and 0.118) that are not consistent with the reported **mortality rates** of 14.4% and 16.7%. - These values do not represent the **Absolute Risk Reduction** required for calculating NNT in this specific scenario.

Number needed to treat/harm Flashcard 1 of 10

Question: _____ is used to model the linear relationship between a dependent variable and an independent variable

Answer: Linear regression

Number needed to treat/harm Flashcard 2 of 10

Question: Lead-time bias can be reduced by measuring _____

Answer: "back-end" survival

Number needed to treat/harm Flashcard 3 of 10

Question: _____ risk reduction is the proportion of risk reduction attributable to an intervention compared to a control

Answer: Relative

Number needed to treat/harm Flashcard 4 of 10

Question: Specificity values approaching 100% is desirable for ruling _____ disease (in or out)

Answer: IN

Number needed to treat/harm Flashcard 5 of 10

Question: The number needed to harm (NNH) is equal to _____

Answer: 1/AR

Number needed to treat/harm Flashcard 6 of 10

Question: A method of statistical analysis that pools summary data (ex. means, RRs) from multiple studies for a more precise estimate of the size of an effect is known as _____

Answer: meta-analysis

Number needed to treat/harm Flashcard 7 of 10

Question: _____ ratios can be multiplied with pretest odds of disease to estimate posttest odds

Answer: Likelihood

Number needed to treat/harm Flashcard 8 of 10

Question: attributable risk/absolute risk reduction (epidemiology)

Answer: the difference in risk between exposed and unexposed groups (attributable risk used for risk-enhancing factors ARR used for risk-reducing interventions)

Number needed to treat/harm Flashcard 9 of 10

Question: number needed to harm (NNH) (epidemiology)

Answer: The number of patients who must be exposed in order to cause 1 event.

Extra Information: NNH = 1/attributable risk

Number needed to treat/harm Flashcard 10 of 10

Question: number needed to treat (NNT) (epidemiology)

Answer: The number of patients who must be treated in order to prevent 1 event.

Extra Information: NNT = 1/absolute risk reduction