Power and sample size

Power and sample size US Medical PG Question 1: A 21-year-old man presents to the office for a follow-up visit. He was recently diagnosed with type 1 diabetes mellitus after being hospitalized for diabetic ketoacidosis following a respiratory infection. He is here today to discuss treatment options available for his condition. The doctor mentions a recent study in which researchers have developed a new version of the insulin pump that appears efficacious in type 1 diabetics. They are currently comparing it to insulin injection therapy. This new pump is not yet available, but it looks very promising. At what stage of clinical trials is this current treatment most likely at?

• A. Phase 0
• B. Phase 2
• C. Phase 3 (Correct Answer)
• D. Phase 1
• E. Phase 4

Power and sample size Explanation: ***Phase 3*** - **Phase 3 trials** involve large-scale studies comparing the new treatment to standard therapy or placebo, often across multiple centers. - The scenario describes a "new version of the insulin pump" being compared to "insulin injection therapy," indicating a definitive comparison for efficacy and safety against existing treatments. *Phase 0* - **Phase 0 trials** are exploratory, small-scale studies (10-15 subjects) using micro-doses to gather preliminary data on pharmacodynamics and pharmacokinetics, not efficacy comparisons. - They are typically conducted very early in drug development, examining if the drug behaves as expected in humans. *Phase 2* - **Phase 2 trials** evaluate the efficacy and further assess safety of a new treatment in a larger group of patients (tens to hundreds). - While they assess efficacy, they usually don't involve direct comparison with an established standard therapy on the scale implied by the question, which is typically reserved for Phase 3. *Phase 1* - **Phase 1 trials** primarily focus on safety, dosage, and side effects in a small group of healthy volunteers or patients with the condition (20-100 subjects). - These trials are not designed to assess a treatment's efficacy against an existing therapy. *Phase 4* - **Phase 4 trials** occur after a drug or device has been approved and marketed, focusing on long-term safety, effectiveness in diverse populations, and new indications. - The described pump "is not yet available," indicating it has not reached the market and thus is not in Phase 4.

Power and sample size US Medical PG Question 2: An investigator is measuring the blood calcium level in a sample of female cross country runners and a control group of sedentary females. If she would like to compare the means of the two groups, which statistical test should she use?

• A. Chi-square test
• B. Linear regression
• C. t-test (Correct Answer)
• D. ANOVA (Analysis of Variance)
• E. F-test

Power and sample size Explanation: ***t-test*** - A **t-test** is appropriate for comparing the means of two independent groups, such as the blood calcium levels between runners and sedentary females. - It assesses whether the observed difference between the two sample means is statistically significant or occurred by chance. *Chi-square test* - The **chi-square test** is used to analyze categorical data to determine if there is a significant association between two variables. - It is not suitable for comparing continuous variables like blood calcium levels. *Linear regression* - **Linear regression** is used to model the relationship between a dependent variable (outcome) and one or more independent variables (predictors). - It aims to predict the value of a variable based on the value of another, rather than comparing means between groups. *ANOVA (Analysis of Variance)* - **ANOVA** is used to compare the means of **three or more independent groups**. - Since there are only two groups being compared in this scenario, a t-test is more specific and appropriate. *F-test* - The **F-test** is primarily used to compare the variances of two populations or to assess the overall significance of a regression model. - While it is the basis for ANOVA, it is not the direct test for comparing the means of two groups.

Power and sample size US Medical PG Question 3: 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

Power and sample size 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.

Power and sample size US Medical PG Question 4: 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)

Power and sample size 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.

Power and sample size US Medical PG Question 5: An epidemiologist is evaluating the efficacy of Noxbinle in preventing HCC deaths at the population level. A clinical trial shows that over 5 years, the mortality rate from HCC was 25% in the control group and 15% in patients treated with Noxbinle 100 mg daily. Based on this data, how many patients need to be treated with Noxbinle 100 mg to prevent, on average, one death from HCC?

• A. 20
• B. 73
• C. 10 (Correct Answer)
• D. 50
• E. 100

Power and sample size Explanation: ***10*** - The **number needed to treat (NNT)** is calculated by first finding the **absolute risk reduction (ARR)**. - **ARR** = Risk in control group - Risk in treatment group = 25% - 15% = **10%** (or 0.10). - **NNT = 1 / ARR** = 1 / 0.10 = **10 patients**. - This means that **10 patients must be treated with Noxbinle to prevent one death from HCC** over 5 years. *20* - This would result from an ARR of 5% (1/0.05 = 20), which is not supported by the data. - May arise from miscalculating the risk difference or incorrectly halving the actual ARR. *73* - This value does not correspond to any standard calculation of NNT from the given mortality rates. - May result from confusion with other epidemiological measures or calculation error. *50* - This would correspond to an ARR of 2% (1/0.02 = 50), which significantly underestimates the actual risk reduction. - Could result from incorrectly calculating the difference as a proportion rather than absolute percentage points. *100* - This would correspond to an ARR of 1% (1/0.01 = 100), grossly underestimating the treatment benefit. - May result from confusing ARR with relative risk reduction or other calculation errors.

Power and sample size Flashcard 1 of 5

Question: The power of a study is increased with _____ sample size

Answer: increased

Power and sample size Flashcard 2 of 5

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

Power and sample size Flashcard 3 of 5

Question: The statistical power of a study is calculated by _____

Answer: 1- beta

Power and sample size Flashcard 4 of 5

Question: What type of study is at the pinnacle of the hierarchy of medical evidence?_____

Answer: Meta analysis

Power and sample size Flashcard 5 of 5

Question: What is the t-test used for? (biostatistics)

Answer: Compare means of two groups. mnemonic: Mr. T is mean.