RCTs

RCTs 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

RCTs 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.

RCTs US Medical PG Question 2: A researcher is conducting a study to compare fracture risk in male patients above the age of 65 who received annual DEXA screening to peers who did not receive screening. He conducts a randomized controlled trial in 900 patients, with half of participants assigned to each experimental group. The researcher ultimately finds similar rates of fractures in the two groups. He then notices that he had forgotten to include 400 patients in his analysis. Including the additional participants in his analysis would most likely affect the study's results in which of the following ways?

• A. Wider confidence intervals of results
• B. Increased probability of committing a type II error
• C. Decreased significance level of results
• D. Increased external validity of results
• E. Increased probability of rejecting the null hypothesis when it is truly false (Correct Answer)

RCTs Explanation: ***Increased probability of rejecting the null hypothesis when it is truly false*** - Including more participants increases the **statistical power** of the study, making it more likely to detect a true effect if one exists. - A higher sample size provides a more precise estimate of the population parameters, leading to a greater ability to **reject a false null hypothesis**. *Wider confidence intervals of results* - A larger sample size generally leads to **narrower confidence intervals**, as it reduces the standard error of the estimate. - Narrower confidence intervals indicate **greater precision** in the estimation of the true population parameter. *Increased probability of committing a type II error* - A **Type II error** (false negative) occurs when a study fails to reject a false null hypothesis. - Increasing the sample size typically **reduces the probability of a Type II error** because it increases statistical power. *Decreased significance level of results* - The **significance level (alpha)** is a pre-determined threshold set by the researcher before the study begins, typically 0.05. - It is independent of sample size and represents the **acceptable probability of committing a Type I error** (false positive). *Increased external validity of results* - **External validity** refers to the generalizability of findings to other populations, settings, or times. - While a larger sample size can enhance the representativeness of the study population, external validity is primarily determined by the **sampling method** and the study's design context, not just sample size alone.

RCTs US Medical PG Question 3: A researcher is trying to determine whether a newly discovered substance X can be useful in promoting wound healing after surgery. She conducts this study by enrolling the next 100 patients that will be undergoing this surgery and separating them into 2 groups. She decides which patient will be in which group by using a random number generator. Subsequently, she prepares 1 set of syringes with the novel substance X and 1 set of syringes with a saline control. Both of these sets of syringes are unlabeled and the substances inside cannot be distinguished. She gives the surgeon performing the surgery 1 of the syringes and does not inform him nor the patient which syringe was used. After the study is complete, she analyzes all the data that was collected and performs statistical analysis. This study most likely provides which level of evidence for use of substance X?

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

RCTs Explanation: ***Level 1*** - The study design described is a **randomized controlled trial (RCT)**, which is considered the **highest level of evidence (Level 1)** in the hierarchy of medical evidence. - Key features like **randomization**, **control group**, and **blinding (double-blind)** help minimize bias and strengthen the validity of the findings. *Level 2* - Level 2 evidence typically comprises **well-designed controlled trials without randomization** (non-randomized controlled trials) or **high-quality cohort studies**. - While strong, they do not possess the same level of internal validity as randomized controlled trials. *Level 3* - Level 3 evidence typically includes **case-control studies** or **cohort studies**, which are observational designs and carry a higher risk of bias compared to RCTs. - These studies generally do not involve randomization or intervention assignment by the researchers. *Level 4* - Level 4 evidence is usually derived from **case series** or **poor quality cohort and case-control studies**. - These studies provide descriptive information or investigate associations without strong control for confounding factors. *Level 5* - Level 5 evidence is the **lowest level of evidence**, consisting of **expert opinion** or **animal research/bench research**. - This level lacks human clinical data or systematic investigative rigor needed for higher evidence levels.

RCTs 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)

RCTs 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.

RCTs US Medical PG Question 5: Which of the following study designs would be most appropriate to investigate the association between electronic cigarette use and the subsequent development of lung cancer?

• A. Subjects with lung cancer who smoke and subjects with lung cancer who did not smoke
• B. Subjects who smoke electronic cigarettes and subjects who smoke normal cigarettes
• C. Subjects with lung cancer who smoke and subjects without lung cancer who smoke
• D. Subjects with lung cancer and subjects without lung cancer
• E. Subjects who smoke electronic cigarettes and subjects who do not smoke (Correct Answer)

RCTs Explanation: ***Subjects who smoke electronic cigarettes and subjects who do not smoke*** - This design represents a **cohort study**, which is ideal for investigating the **incidence** of a disease (lung cancer) in groups exposed and unexposed to a risk factor (electronic cigarette use). - By following these two groups over time, researchers can directly compare the **risk of developing lung cancer** in e-cigarette users versus non-smokers. *Subjects with lung cancer who smoke and subjects with lung cancer who did not smoke* - This option incorrectly compares two groups both with lung cancer, where the exposure to smoking can either be **electronic or traditional cigarettes,** but does not provide a control group without lung cancer to assess the association. - This design would not allow for the calculation of an **incidence rate** or a **relative risk** of lung cancer development specific to electronic cigarette use. *Subjects who smoke electronic cigarettes and subjects who smoke normal cigarettes* - This design compares two different types of smoking, which might be useful for comparing their relative risks but doesn't include a **non-smoking control group** to establish the absolute association with electronic cigarettes. - While it could show if e-cigarettes are "safer" than traditional cigarettes, it wouldn't directly answer whether e-cigarettes themselves **cause lung cancer**. *Subjects with lung cancer who smoke and subjects without lung cancer who smoke* - This describes a **case-control study** but focuses on smoking in general rather than specifically electronic cigarettes, which is the independent variable of interest. - While valuable for identifying risk factors, it would need to specifically differentiate between **electronic cigarette smokers** and other smokers to answer the question adequately. *Subjects with lung cancer and subjects without lung cancer* - This general description of a **case-control study** is too broad; it does not specify the exposure of interest, which is electronic cigarette use. - To be relevant, the study would need to gather data on **electronic cigarette use** in both the lung cancer group and the non-lung cancer control group.

RCTs US Medical PG Question 6: 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

RCTs 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.

RCTs US Medical PG Question 7: You are currently employed as a clinical researcher working on clinical trials of a new drug to be used for the treatment of Parkinson's disease. Currently, you have already determined the safe clinical dose of the drug in a healthy patient. You are in the phase of drug development where the drug is studied in patients with the target disease to determine its efficacy. Which of the following phases is this new drug currently in?

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

RCTs Explanation: ***Phase 2*** - **Phase 2 trials** involve studying the drug in patients with the target disease to assess its **efficacy** and further evaluate safety, typically involving a few hundred patients. - The question describes a stage after safe dosing in healthy patients (Phase 1) and before large-scale efficacy confirmation (Phase 3), focusing on efficacy in the target population. *Phase 4* - **Phase 4 trials** occur **after a drug has been approved** and marketed, monitoring long-term effects, optimal use, and rare side effects in a diverse patient population. - This phase is conducted post-market approval, whereas the question describes a drug still in development prior to approval. *Phase 1* - **Phase 1 trials** primarily focus on determining the **safety and dosage** of a new drug in a **small group of healthy volunteers** (or sometimes patients with advanced disease if the drug is highly toxic). - The question states that the safe clinical dose in a healthy patient has already been determined, indicating that Phase 1 has been completed. *Phase 0* - **Phase 0 trials** are exploratory, very early-stage studies designed to confirm that the drug reaches the target and acts as intended, typically involving a very small number of doses and participants. - These trials are conducted much earlier in the development process, preceding the determination of safe clinical doses and large-scale efficacy studies. *Phase 3* - **Phase 3 trials** are large-scale studies involving hundreds to thousands of patients to confirm **efficacy**, monitor side effects, compare it to commonly used treatments, and collect information that will allow the drug to be used safely. - While Phase 3 does assess efficacy, it follows Phase 2 and is typically conducted on a much larger scale before submitting for regulatory approval.

RCTs US Medical PG Question 8: 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?

• A. "Does the diarrhea typically precede the constipation, or vice-versa?"
• B. "Is the diarrhea foul-smelling?"
• C. "Please rate your abdominal pain on a scale of 1-10, with 10 being the worst pain of your life"
• D. "Are the symptoms worse in the morning or at night?"
• E. "Can you tell me more about the symptoms you have been experiencing?" (Correct Answer)

RCTs Explanation: ***Can you tell me more about the symptoms you have been experiencing?*** - This **open-ended question** encourages the patient to provide a **comprehensive narrative** of their symptoms, including details about onset, frequency, duration, alleviating/aggravating factors, and associated symptoms, which is crucial for diagnosis. - In a patient presenting with vague, intermittent symptoms like alternating constipation and diarrhea, allowing them to elaborate freely can reveal important clues that might not be captured by more targeted questions. *Does the diarrhea typically precede the constipation, or vice-versa?* - While knowing the sequence of symptoms can be helpful in understanding the **pattern of bowel dysfunction**, it is a very specific question that might overlook other important aspects of the patient's experience. - It prematurely narrows the focus without first obtaining a broad understanding of the patient's overall symptomatic picture. *Is the diarrhea foul-smelling?* - Foul-smelling diarrhea can indicate **malabsorption** or **bacterial overgrowth**, which are important to consider in some gastrointestinal conditions. - However, this is a **specific symptom inquiry** that should follow a more general exploration of the patient's symptoms, as it may not be relevant if other crucial details are missed. *Please rate your abdominal pain on a scale of 1-10, with 10 being the worst pain of your life* - Quantifying pain intensity is useful for assessing the **severity of discomfort** and monitoring changes over time. - However, for a patient with intermittent rather than acute, severe pain, understanding the **character, location, and triggers** of the pain is often more diagnostically valuable than just a numerical rating initially. *Are the symptoms worse in the morning or at night?* - Diurnal variation can be relevant in certain conditions, such as inflammatory bowel diseases where nocturnal symptoms might be more concerning, or functional disorders whose symptoms might be stress-related. - This is another **specific question** that should come after gathering a more complete initial picture of the patient's symptoms to ensure no key information is overlooked.

RCTs US Medical PG Question 9: A clinical trial is conducted to determine the efficacy of ginkgo biloba in the treatment of Parkinson disease. A sample of patients with Parkinson disease is divided into two groups. Participants in the first group are treated with ginkgo biloba, and participants in the other group receive a placebo. A change in the Movement Disorder Society-Unified Parkinson Disease Rating Scale (MDS-UPDRS) score is used as the primary endpoint for the study. The investigators, participants, and data analysts were meant to be blinded throughout the trial. However, while the trial is being conducted, the patients' demographics and their allocated treatment groups are mistakenly disclosed to the investigators, but not to the participants or the data analysts, because of a technical flaw. The study concludes that there is a significant decrease in MDS-UPDRS scores in patients treated with ginkgo biloba. Which of the following is most likely to have affected the validity of this study?

• A. Effect modification
• B. Recall bias
• C. Pygmalion effect (Correct Answer)
• D. Hawthorne effect
• E. Procedure bias

RCTs Explanation: ***Pygmalion effect*** - The **Pygmalion effect**, also known as **observer-expectancy bias** or experimenter bias, occurs when an investigator's expectations about the outcome of a study unintentionally influence the results. - In this case, the **investigators becoming unblinded** to treatment assignments could lead them to unconsciously influence patient assessments or interactions based on their knowledge of who received ginkgo biloba, potentially leading to inflated positive outcomes for the treatment group. *Effect modification* - **Effect modification** describes a phenomenon where the effect of an exposure on an outcome is different across various strata of a third variable. - This is a true biological interaction and does not represent a bias or flaw in the study design due to unblinding. *Recall bias* - **Recall bias** occurs when participants' memories of past exposures or events differ based on their current health status or knowledge of their condition. - This bias primarily affects studies that rely on **retrospective reporting** of past events and is not relevant to the unblinding of investigators in a prospective clinical trial. *Hawthorne effect* - The **Hawthorne effect** describes a phenomenon where participants in a study change their behavior simply because they are aware of being observed, regardless of the intervention they receive. - While participant blinding is important to prevent this, the scenario describes investigators being unblinded, not the participants. *Procedure bias* - **Procedure bias** (also known as interviewer bias or performance bias) arises from systematic differences in the way data is collected or procedures are performed for different study groups. - While investigator unblinding can lead to elements of procedure bias, the more specific and encompassing term for an investigator's expectations influencing results is the **Pygmalion effect** (observer-expectancy bias).

RCTs US Medical PG Question 10: 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)

RCTs 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.

RCTs Flashcard 1 of 8

Question: Are Randomization and Concealment the same? _____

Answer: nah bruh

RCTs Flashcard 2 of 8

Question: Randomization is critical in preventing _____

Answer: confounding bias

RCTs Flashcard 3 of 8

Question: The number needed to treat (NNT) is equal to _____

Answer: 1/ARR

RCTs Flashcard 4 of 8

Question: Phase III

Answer: Large numbers of people with the disease of interest; RCT format

Extra Information: Compares new treatment to existing standard of care

RCTs Flashcard 5 of 8

Question: Are Randomization and Concealment the same? _____

Answer: nah bruh

Extra Information:  https://onlinemeded.org/spa/epidemiology-and-stats/bias/acquire?ref=anki  

RCTs Flashcard 6 of 8

Question: Concealment is critical in preventing _____

Answer: selection bias

Extra Information:  https://onlinemeded.org/spa/epidemiology-and-stats/bias/acquire?ref=anki 

RCTs Flashcard 7 of 8

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

Answer: Relative

RCTs Flashcard 8 of 8

Question: Blinding (the cardinal feature of RCTs) is critical in reducing _____

Answer: measurement bias