Module 9

Question 1

What is one defining feature of experimental studies?

Answer 1

Manipulation of tx or exposure

Question 2

What is the study called when the unit of analysis is the individual?

Answer 2

Randomized clinical trials

Question 3

What is the study called when the unit of analysis is groups?

Answer 3

Community interventions

Question 4

Characteristics of epidemiologic experimental studies

Answer 4

Resemble controlled experiments performed in scientific research
Assignment of exposure done randomly by investigator
Best for establishing cause-effect relationships and for evaluating the efficacy of preventive and therapeutic interventions

Question 5

Characteristics of quasi-experimental experiments

Answer 5

Ranked immediately below controlled experiments in rigor
Investigator is unable to randomly allocate participants to the study conditions (tx or control group)
Because of this, the intervention and control groups may differ in ways other than the presence or absence of the intervention

Question 6

Clinical trials definition

Answer 6

A planned experiment that assesses the efficacy of a tx or preventative intervention in humans
Randomized control trials are the gold standard to which other studies are compared

Question 7

Design of a clinical trial

Answer 7

The unit of analysis is the individual
Prospective: follow at least two groups forward in time
-Tx and control groups
-Participants in both groups are enrolled, treated, and followed over the same time period.
Intervention is compared with placebo or usual care
-Investigator controls/manipulates conditions studied
-Investigator assigns exposure (tx) randomly
Outcomes in treated group are compared with outcomes in an equivalent control group

Question 8

Details about first clinical trial

Answer 8

James Lind in 1747 applied experimental methods to discover that eating citrus fruits was an effective remedy for scurvy among sailors at sea

Question 9

What makes a randomized clinical trial superior to the other study designs?

Answer 9

The experimental nature

Question 10

Details about random assignment

Answer 10

Makes intervention and control groups look as similar as possible
Chance is the only factor that determines group assignment
Neither the patient nor the physician know in advance which prevention program or therapy will be assigned

Question 11

Details about randomization

Answer 11

Purpose is to prevent a form of bias called “confounding bias”
Method of choice for assigning participants to the tx or control conditions of a clinical trial
Guarantees that tx assignment is not based on pt prognostic factors (anything else that may influence the outcome)

Question 12

Details about quasi-experiment

Answer 12

Concurrent comparison group is allocated by a nonrandom process (convenience sample)
Non-random assignment may cause mixing of the effects of the intervention with differences among the participants of the trial
The tx and control groups may be different in ways extraneous to whether they get the intervention or not (such as age)

Question 13

What are the two main types of clinical trials?

Answer 13

Prophylactic and therapeutic trials

Question 14

Prophylactic trial purpose

Answer 14

Evaluates the effectiveness of a substance that is used to prevent dz; it can also form a prevention program. It is a test of a form of primary prevention

Question 15

Therapeutic trail purpose

Answer 15

Involves the study of curative drugs or a new surgical procedure to improve the pt’s health. It is a test of a form of secondary or tertiary prevention.

Question 16

Definition of crossover designs

Answer 16

Any change of tx for a pt in a clinical trial involving a switch of study txs

Question 17

Planned crossovers

Answer 17

A protocol (plan) is developed in advance, and the pt may serve as his/her/their own control

Question 18

Unplanned crossovers

Answer 18

Exist for various reasons, such as the pt’s request to change tx

Question 19

Phase I of clinical trial

Answer 19

To learn about the safety of drug, tx, or vaccine.
In adult volunteers (<100 volunteers)
Drug dosage
Side effects

Question 20

Phase II of clinical trial

Answer 20

To learn if the drug, tx, or vaccine works
Expands testing to a group of 100 to 200 participants (from the source population)
May include a control group
Examine antibody responses and clinical reactions

Question 21

Phase III of a clinical trial

Answer 21

To learn if the drug, tx, or vaccine is better than usual care
(the main test) assesses the efficacy of the vaccine in the source pop (possibly thousands of participants)
Now must include at least one control group
Goes up for FDA approval

Question 22

Phase IV of a clinical trial

Answer 22

To learn what else may need to be known
Only after FDA approval
Studies very long term effects in large groups of ppl

Question 23

What question does efficacy ask?

Answer 23

Can the tx work under ideal conditions?
Established by restricting study to pts who will follow medical advice

Question 24

What question does effectiveness ask?

Answer 24

Can the tx work under normal (ordinary) conditions?
Established by offering tx to pts and allowing them to decide to accept or reject it
If tx ineffective, could be d/t lack of efficacy or to lack of compliance

Question 25

Compliance definition

Answer 25

Extent to which pts follow medical advice Intervenes between an efficacious tx and an effective one Not just willful neglect of advice Failure to understand instructions Failure to keep prescriptions filled Can limit effectiveness regardless of efficacy

Question 26

What are the types of bias in clinical trials?

Answer 26

Placebo effect Hawthorne effect Interviewer/abstractor bias Loss to follow-up bias

Question 27

Placebo effect definition

Answer 27

The effect on pt outcomes (improved or worsened) that may occur d/t the expectation by a pt that a particular intervention will have an effect

Question 28

Hawthorne effect definition

Answer 28

The process of being observed (or studied) itself brings about behavior change in the participants and influences the results

Question 29

Interviewer/abstractor bias definition

Answer 29

Occurs when interviewers probe more thoroughly in the tx group than in the controls (or any two comparison groups)

Question 30

Loss to f/u bias definition

Answer 30

Can occur when many participants are lost to f/u over time and are not included in the analysis of data at the end, and those lost to follow up differ systematically from the ones who are left.

Question 31

Blinding definition

Answer 31

An attempt to control or prevent some forms of bias in clinical trials There can be: Single blinded studies Double blinded studies

Question 32

Details about single blinded study

Answer 32

The participants are blinded, but investigators are aware of who is receiving the active tx? Why blind pts? -Pts try to get well/please physicians -Minimize potential bias from a placebo effect -Placebos improve comparability of tx groups in terms of compliance and f/u

Question 33

How placebo is carried out in clinical trials

Answer 33

Pill of same size, color, shape as tx Sham operation (anesthesia and incision)

Question 34

Double blind study definition

Answer 34

Neither the participants nor the investigators know who is receiving the active tx

Question 35

Benefits of double blind study

Answer 35

Best way to avoid unconscious bias -Physicians don't know which pt is taking the placebo and which pt is taking the drug -Assessors of outcome are not the treating doctors and are not told which tx was used

Question 36

Problems with blinding

Answer 36

For non-drug studies such as those involving behavior changes or surgery, it may be impossible or unethical to blind It may also be problematic to blind in drug studies where a tx has characteristic side effects

Question 37

Loss to follow up bias details

Answer 37

A common problem in clinical trials and cohort studies, increasingly so in cohorts with longer f/u times Can bias the results, if the percentage lost to f/u is large, and those lost to f/u are different from those who remain with respect to the outcomes being measured

Question 38

Reasons for loss to f/u

Answer 38

Refusal to participate Unable to locate Unable to be interviewed Death

Question 39

Clinical endpoint details

Answer 39

In a clinical trial, the outcomes are referred to as clinical endpoints May include incidence rates of dz, death rates, recovery rates, reoccurrence rates, or increased survival time Outcomes must be measured in a comparable manner in the intervention and control groups

Question 40

Exposure definition

Answer 40

The experimental tx or intervention that has been assigned to one group

Question 41

Relative risk definition

Answer 41

The ratio of the incidence of the clinical endpoint (or outcome) in the exposed or tx group to the incidence of the clinical endpoint in the non-exposed or placebo group

Question 42

Relative risk formula

Answer 42

Relative risk= incidence (or mortality) rate in the treated/incidence (or mortality) rate in the controls [a/(a +b)]/[c/(c+d)]

Question 43

Precise interpretation statement for relative risk

Answer 43

The exposed or tx group were RR times as likely as the non-exposed or placebo group to develop the dz, die, or recover

Question 44

Sample of Nazi medical experiments that were not ethical

Answer 44

Twin and genetic experiment (of 1500 sets of twins, only 100 remained alive) Spotted fever experiments - >90% died -Injected with the dz agent and then experimental "cures" tested Similar experiments with yellow fever, smallpox, typhus, TB Seawater experiments (given seawater to drink) Freezing and hypothermia experiments Sterilization experiments Others

Question 45

Principles of the Nuremberg code of 1949

Answer 45

Human subject should provide voluntary consent and know the risks of participation The experimental results must be for the greater good of experimentation Experiment should be based on previous animal experimentation Experiment should avoid unnecessary physical/mental suffering No experiments should be conducted if it is believed to cause death/disability Benefits must always outweigh risks Adequate facilities should be used to protect subjects Experiment should be conducted only by qualified scientists Subject should always be at liberty to stop at any time Scientist in charge must be prepared to terminate the experiment when injury, disability, or death is likely to occur

Question 46

Tuskegee Syphilis Study (1932-72) and the Belmont Report (1979)

Answer 46

Respect for persons: protect the autonomy of all ppl, treat them with courtesy and respect, allow for informed consent, be truthful and conduct no deception Beneficence: follow philosophy of "do no harm", while maximizing benefits to research project and minimizing risks to participants Justice: fair and equal distribution of costs and benefits to potential research participants

Question 47

Ethical aspects of human experimentation

Answer 47

Informed and voluntary consent Withholding beneficial tx from control group -Crossover designs are used as a solution Monitoring for harmful SEs in tx group -Can be circumvented using animals Deciding when to withdraw an individual pt Deciding when to stop the entire study -Depends on degree of uncertainty Vulnerable groups -Children -Prisoners -Intellectually challenged -Poor, homeless

Question 48

What must be true to ethically continue a trial?

Answer 48

Benefits must always outweigh the risks There must still be uncertainty about the effects of the tx

Question 49

Advantages of clinical trials

Answer 49

Most scientifically rigorous design for evaluating the effect of a single, controlled exposure or intervention Ability to randomize reduces the likelihood that groups will differ significantly on factors other than the tx, that may influence the results, such as age. Less potential for bias than observational studies The best of all studies for establishing cause and effect (causality) Reproducible Provide the greatest control over: -The amt of exposure -The timing and frequency of exposure -The period of observation

Question 50

Limitations of clinical trials

Answer 50

Ethical considerations may limit: -Selection of participants -Generalizability of results -Type of exposures studied: not for harmful exposures Applicable only to certain types of research questions, at a particular stage of knowledge about the problem Expensive Complex planning Adherence to protocol is difficult to enforce -Compliance issues Artificial setting Generalizability may be limited

Question 51

Group assignments in Lind clinical trial

Answer 51

Each group had 2 people who already had scurvy 1: A quart of cider daily 2: An unspecified elixir 3 times/day 3: Seawater 4: Garlic, mustard, horseradish 5: Spoonful of vinegar 6: 2 oranges and a lemon daily In six days, only group 2 was fit for duty

Question 52

What are the two types of interventional studies?

Answer 52

Randomized control clinical trials Community interventions

Question 53

What are multi-center trials?

Answer 53

Results from several researchers are pooled.

Question 54

Are multi-center trials randomized control trials or community interventions? Why?

Answer 54

Randomized control trials because the unit of analysis is the individual