Study designs

Study designs US Medical PG Question 1: A researcher is studying whether a new knee implant is better than existing alternatives in terms of pain after knee replacement. She designs the study so that it includes all the surgeries performed at a certain hospital. Interestingly, she notices that patients who underwent surgeries on Mondays and Thursdays reported much better pain outcomes on a survey compared with those who underwent the same surgeries from the same surgeons on Tuesdays and Fridays. Upon performing further analysis, she discovers that one of the staff members who works on Mondays and Thursdays is aware of the study and tells all the patients about how wonderful the new implant is. Which of the following forms of bias does this most likely represent?

• A. Hawthorne effect
• B. Pygmalion effect (Correct Answer)
• C. Attrition bias
• D. Golem effect

Study designs Explanation: ***Pygmalion effect*** - This bias occurs when higher expectations lead to an increase in performance. In this scenario, the staff member's positive reinforcement about the new implant likely instilled **higher patient expectations**, leading to better reported pain outcomes. - The patients' belief in the implant's superiority, influenced by the staff member, acted as a **self-fulfilling prophecy**, improving their subjective pain experience. *Hawthorne effect* - This effect describes how individuals modify an aspect of their behavior in response to their awareness of being observed. While patients were part of a study, their improved outcomes were specifically linked to a staff member's verbal influence, not solely the act of observation. - The improved pain outcomes stem from the **expectations created by the staff member's praise**, rather than a general awareness of being studied. *Attrition bias* - Attrition bias refers to systematic differences between groups in the loss of participants from a study. - This scenario describes differences in patient outcomes based on staff influence during the study, not due to **patients dropping out differentially** between groups. *Golem effect* - The Golem effect is the opposite of the Pygmalion effect, where lower expectations placed upon individuals lead to poorer performance from them. - In this case, the staff member's influence created **high expectations and positive outcomes**, not negative expectations leading to worse outcomes.

Study designs US Medical PG Question 2: A 42-year-old woman presents to the physician with symptoms of vague abdominal pain and bloating for several months. Test results indicate that she has ovarian cancer. Her physician attempts to reach her by phone multiple times but cannot reach her. Next of kin numbers are in her chart. According to HIPAA regulations, who should be the primary person the doctor discusses this information with?

• A. The patient's brother
• B. The patient's husband
• C. The patient's daughter
• D. All of the options
• E. The patient (Correct Answer)

Study designs Explanation: ***The patient*** - Under **HIPAA**, the patient has the **right to privacy** regarding their protected health information (PHI). Therefore, the physician must make all reasonable attempts to contact the patient directly to convey their diagnosis. - Sharing sensitive medical information like a cancer diagnosis with anyone other than the patient, without their explicit consent, would be a **violation of HIPAA regulations**. *The patient's brother* - The patient's brother is not automatically authorized to receive her medical information, even if listed as **next of kin**, without the patient's explicit consent or a documented **healthcare power of attorney**. - Discussing the diagnosis with the brother without the patient's direct consent would be a **breach of patient confidentiality**. *The patient's husband* - Even a spouse does not automatically have the right to access a patient's **PHI** without the patient's express permission, according to **HIPAA**. - While often a trusted contact, without explicit consent, revealing the diagnosis to the husband would still violate the patient's **privacy rights**. *The patient's daughter* - Similar to other family members, the patient's daughter is not legally entitled to receive her mother's confidential medical information without explicit authorization or a medical **power of attorney**. - The physician's primary responsibility is to the patient herself, ensuring her **privacy** is maintained. *All of the options* - According to **HIPAA**, sharing the patient's diagnosis with any family member without her explicit consent would be a **breach of confidentiality**. - This option incorrectly assumes that **next of kin** automatically have the right to receive sensitive medical information.

Study designs US Medical PG Question 3: 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)

Study designs 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.

Study designs US Medical PG Question 4: 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

Study designs 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.

Study designs US Medical PG Question 5: A pharmaceutical corporation has asked you to assist in the development of a randomized controlled trial (RCT) to evaluate the response of renal cell carcinoma to a novel chemotherapeutic agent. Despite all of the benefits that an RCT has to offer, which of the following would make an RCT unacceptable with regard to study design?

• A. Proper treatment response is very common
• B. The treatment is not widespread in use
• C. The treatment does not represent the best known option
• D. The treatment is expensive
• E. The treatment has a known, adverse outcome (Correct Answer)

Study designs Explanation: ***The treatment has a known, adverse outcome*** - If a treatment is already known to cause **significant harm** or an adverse outcome, it would be unethical to randomize patients to receive it, as this would expose them to unnecessary risk. - **Ethical considerations** are paramount in clinical trial design; exposing patients to a known harmful treatment violates the principle of non-maleficence. *Proper treatment response is very common* - A high treatment response rate would make it **easier to detect a difference** between the novel agent and a control group, potentially requiring a smaller sample size. - This scenario actually **facilitates** an RCT, as it increases the likelihood of demonstrating efficacy for the novel agent. *The treatment is not widespread in use* - The purpose of an RCT for a novel agent is precisely to evaluate its efficacy and safety to determine if it **deserves widespread use**. - Lack of widespread use is the **starting point** for clinical trials, not a contraindication. *The treatment does not represent the best known option* - An RCT is often conducted to determine if a novel treatment is **superior or non-inferior** to existing standard-of-care treatments, even if the existing options are not considered "the best." - Comparing a new treatment against a suboptimal current standard is a common and **valid objective** in clinical research to seek improvement. *The treatment is expensive* - The cost of a treatment is a **practical consideration** for healthcare systems and patients but does not inherently make an RCT unacceptable in terms of study design or ethics. - **Cost-effectiveness** is often evaluated after efficacy and safety are established, usually in addition to the RCT or in subsequent studies.

Study designs US Medical PG Question 6: 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)

Study designs 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.

Study designs US Medical PG Question 7: 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)

Study designs 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.

Study designs US Medical PG Question 8: A 73-year-old man is brought to the emergency department by ambulance after being found to be non-communicative by his family during dinner. On presentation he appears to be alert, though he is confused and cannot follow instructions. When he tries to speak, he vocalizes a string of fluent but unintelligible syllables. Given this presentation, his physician decides to administer tissue plasminogen activator to this patient. This intervention best represents which of the following principles?

• A. Tertiary prevention
• B. Primary prevention
• C. This does not represent prevention (Correct Answer)
• D. Quaternary prevention
• E. Secondary prevention

Study designs Explanation: ***This does not represent prevention*** - The administration of **tissue plasminogen activator (tPA)** during an **acute stroke** is a **therapeutic intervention**, not a form of prevention. - **Prevention** refers to actions taken to prevent disease occurrence, detect it early, or prevent complications after recovery. Treating an acute, symptomatic event is **acute treatment**, not prevention. - This is an active medical intervention to treat an ongoing, symptomatic disease process (acute ischemic stroke), which falls under **therapeutic management** rather than any category of prevention. *Secondary prevention* - **Secondary prevention** involves **early detection** and treatment of asymptomatic or minimally symptomatic disease to prevent progression (e.g., screening mammography, colonoscopy). - For stroke specifically, secondary prevention would include interventions **after** the acute event to **prevent recurrence**, such as starting antiplatelet therapy (aspirin, clopidogrel), anticoagulation for atrial fibrillation, statin therapy, or carotid endarterectomy after TIA. - tPA is given during the acute symptomatic phase, making it treatment rather than secondary prevention. *Tertiary prevention* - **Tertiary prevention** focuses on **rehabilitation** and managing established disease to prevent complications and improve quality of life. - Examples after stroke include physical therapy, occupational therapy, speech therapy, and managing post-stroke complications like depression or spasticity. - This occurs in the recovery phase, not during acute treatment. *Primary prevention* - **Primary prevention** aims to prevent disease before it occurs in healthy individuals. - Examples include controlling hypertension, managing diabetes, smoking cessation, exercise, and healthy diet - all interventions that reduce stroke risk **before** any event occurs. *Quaternary prevention* - **Quaternary prevention** protects patients from **overmedicalization** and excessive or harmful medical interventions. - It involves avoiding unnecessary testing or treatment that may cause more harm than benefit. - Administering tPA for acute stroke (when indicated) is evidence-based treatment, not overtreatment.

Study designs US Medical PG Question 9: A research team has data from three completed studies on statin use and Alzheimer's disease: Study A (case-control, OR=0.6, n=500), Study B (retrospective cohort, RR=0.7, n=10,000), and Study C (RCT with cognitive decline as secondary endpoint, RR=0.9, n=2,000). The case-control study used prevalent cases, the cohort study had significant loss to follow-up in the unexposed group, and the RCT was underpowered for cognitive outcomes. Synthesize the evidence to determine the most reliable conclusion about the association.

• A. The RCT provides the strongest evidence despite being underpowered
• B. The retrospective cohort study offers the best balance of validity and precision (Correct Answer)
• C. Case-control study is most reliable due to efficient rare outcome assessment
• D. Evidence is contradictory and no conclusion can be drawn
• E. Meta-analysis of all three studies provides the most accurate estimate

Study designs Explanation: ***The retrospective cohort study offers the best balance of validity and precision*** - Despite **differential loss to follow-up** in the unexposed, the very large **sample size (n=10,000)** provides high **statistical power** and precision compared to the other studies. - Cohort studies establish a **temporal sequence** (statin use before disease onset), which is superior to cross-sectional or prevalent case-control designs for causal inference. *The RCT provides the strongest evidence despite being underpowered* - While **Randomized Controlled Trials (RCTs)** are higher in the evidence hierarchy, an **underpowered** study lacks the precision to detect a true effect, increasing the risk of a **Type II error**. - Since cognitive decline was only a **secondary endpoint**, the study may not have been designed or followed long enough to assess Alzheimer's disease progression accurately. *Case-control study is most reliable due to efficient rare outcome assessment* - The use of **prevalent cases** instead of incident cases introduces **Neyman bias (survival bias)**, as it only includes patients who survived long enough to be studied. - Case-control studies are prone to **recall bias** and cannot definitively prove that statin use preceded the onset of cognitive decline. *Evidence is contradictory and no conclusion can be drawn* - While the results vary, researchers can still synthesize evidence by weighing studies based on their **methodological quality**, **sample size**, and **bias profile**. - A conclusion can be drawn by acknowledging the **conservative estimate** (bias toward the null) in the cohort study which still suggested a protective effect. *Meta-analysis of all three studies provides the most accurate estimate* - **Meta-analysis** of studies with fundamentally different designs (RCT, Cohort, Case-Control) and significant **methodological limitations** can lead to inaccurate pooled results ("garbage in, garbage out"). - Combining studies with different measures of association (OR vs RR) and distinct biases like **survival bias** and **differential attrition** increases **heterogeneity**.

Study designs US Medical PG Question 10: A public health department needs to determine whether a cluster of birth defects in a county is associated with industrial pollution. They have limited resources, the suspected exposure occurred 3-5 years ago, and the outcome is rare (15 cases identified). Multiple potential confounders exist including maternal age, socioeconomic status, and prenatal care access. The community demands rapid answers. Evaluate the most appropriate initial study design considering feasibility, ethics, and scientific validity.

• A. Prospective cohort study of pregnant women with exposure monitoring
• B. Randomized controlled trial comparing exposed and unexposed areas
• C. Case-control study with multiple control groups and confounder adjustment (Correct Answer)
• D. Ecologic study comparing county-level pollution and birth defect rates
• E. Cross-sectional survey of current pollution levels and birth outcomes

Study designs Explanation: ***Case-control study with multiple control groups and confounder adjustment*** - A **case-control study** is the gold standard for investigating **rare outcomes** (only 15 cases identified) because it identifies subjects based on disease status rather than waiting for it to develop. - This design is highly efficient for **retrospective exposures** that occurred years ago, allows for **rapid results** with limited resources, and can adjust for multiple **confounders** like maternal age and SES through statistical modeling. *Prospective cohort study of pregnant women with exposure monitoring* - This design is inappropriate for **rare outcomes** because it would require an massive sample size and many years of follow-up before seeing enough cases to be statistically significant. - It cannot address a **past exposure** (3-5 years ago) as it follows subjects forward in time from the point of current exposure. *Randomized controlled trial comparing exposed and unexposed areas* - It is fundamentally **unethical** to intentionally expose human populations to potentially harmful industrial pollutants in an experimental setting. - RCTs are used for **interventions** (like new drugs) rather than investigating the etiology of environmental health hazards. *Ecologic study comparing county-level pollution and birth defect rates* - This design is prone to the **ecologic fallacy**, where associations found at the population level may not hold true for individuals within that population. - It cannot adjust for **individual-level confounders** such as personal prenatal care access or specific maternal age, making the results scientifically weaker for the community's needs. *Cross-sectional survey of current pollution levels and birth outcomes* - This design suffers from **temporal ambiguity**, as it measures exposure and outcome simultaneously, failing to confirm that pollution Exposure preceded the birth defects. - Current pollution levels may not accurately reflect the **historical exposure** that occurred during the critical window of embryogenesis 3-5 years ago.

Study designs Flashcard 1 of 9

Question: Both twin concordance and adoption studies are useful for measuring '_____'

Answer: nature vs. nurture

Study designs Flashcard 2 of 9

Question: Which type of conditioning usually deals with voluntary responses? _____

Answer: Operant conditioning

Study designs Flashcard 3 of 9

Question: What percent of twins are monozygotic?

Answer: 20%

Study designs Flashcard 4 of 9

Question: What percent of twins are dizygotic?

Answer: 80%

Study designs Flashcard 5 of 9

Question: Explain how a twin concordance study works.

Answer: Compares the frequency with which twins (mono- or dizygotic) develop the same disease.

Study designs Flashcard 6 of 9

Question: What kind of study compares the frequency with which twins develop the same disease?

Answer: Twin concordance study

Study designs Flashcard 7 of 9

Question: Explain how an adoption study works.

Answer: Compares disease outcomes in siblings (especially twins) raised by different parents

Study designs Flashcard 8 of 9

Question: What type of study compares disease outcomes in siblings (especially twins) raised by different parents

Answer: Adoption study

Study designs Flashcard 9 of 9

Question: New baby and toddler is being mean to baby is managed with _____

Answer: mom spending more time with toddler

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