c1, l3-4, s1 types of studies and study design. c1, l3-4, s2 research classifications observational...

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Types of Studies and Study Design

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Research classifications• Observational vs. Experimental

Observational – researcher collects info on attributes or measurements of interest, but does not influence results.

Experimental – researcher deliberately influences events and investigates the effects of the intervention, e.g. clinical trials and laboratory experiments.

We often use these when we are interested in studying the effect of a treatment on individuals or experimental units.

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Experiments & Observational Studies

We conduct an experiment when it is (ethically, physically etc) possible for the experimenter to determine which experimental units receive which treatment.

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Experiments & Observational StudiesExperiment Terminology

Experimental Unit Treatment Response

patient drug cholesterol

patient pre-surgery antibiotic infection

mouse radiation mortality

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In an observational study, we compare the units that happen to have received each of the treatments.

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e.g. You cannot set up a control (non-smoking) group and treatment (smoking) group.

Observational Study

patient smoking lung cancer

RN unit job stresshospital ICU

staffing levelICU mortality


Unit Treatment Response

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Note:

Only a well-designed and well-executed experiment can reliably establish causation.

An observational study is useful for identifying possible causes of effects, but it cannot reliably establish causation.

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1. Completely Randomized Design

The treatments are allocated entirely by

chance to the experimental units.

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Example:

Which of two varieties of tomatoes (A & B) yield a greater quantity of market quality fruit?

Factors that may affect yield:• different soil fertility levels• exposure to wind/sun• soil pH levels• soil water content etc.

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Divide the field into plots and randomly allocate the tomato varieties (treatments) to each plot (unit).

8 plots – 4 get variety A

(A) (A) (A)

(A)(B) (B)

(B)

(B)


What if the field sloped upward from left to right?

UPHILL

(B)

(B)

(B) (B

)(A)

(A)

Randomly assign A & B varieties in each strip of similar elevation.

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Note:

Randomization is an attempt to make the treatment groups as similar as possible — we can only expect to achieve this when there is a large number of experimental units to choose from.

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2. BlockingGroup (block) experimental units by some known factor and then randomize within each block in an attempt to balance out the unknown factors.

Use:•blocking for known factors

(e.g. slope of field in previous example)

and•randomization for unknown factors to try to “balance things out”.

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2. Blocking

Example 2: Multi-Center Clinical Trial

Suppose a Mayo clinical trial comparing two chemotherapy regimens in treatment of patients with colon cancer will be conducted using cancer patients in Scottsdale, AZ and Rochester, MN.

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Scottsdale Rochester

2. Blocking

How should we allocate treatments to the 12 patients?

7 (B)

2 (A)

3 (A)

5 (A) 6 (A)

1 (A)

2 (B)3 (A)

4 (B)

8 (B)

4 (B)

1 (B)

Randomly assign treatments to 4 the patients from Scottsdale and then to the 8 Rochester patients.

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2. Blocking

Example 3: Comparing Three Pain Relievers for Headache Sufferers

• How could blocking be used to increase precision of a designed experiment to control to compare the pain relievers?

• What are some other design issues?

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Example 4: Comparing 17 Different Leg Wraps on Used on Race Horses

• 17 “boots” tested, each boot is tested n = 5 times. Why?

• Because of the time constraints all boots were not tested on the same day.

• 8 tested 1st day, 5 tested 2nd day, 4 tested 3rd day.

• Leg was placed in freezer and thawed before the 2nd and 3rd days of testing.

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Horse Leg Wraps (cont’d)

• What problems do you foresee with this experimental design? Discussion Question 1

• What actually happened?

What are the implications of these results? Discussion Question 2

Forces readings obtained from cadaver leg when no boot or wrap was used.

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Horse Leg Wraps (cont’d)

FINAL BOOT COMPARISONS

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Horse Legs Wraps (cont’d)

• What should have been done?

Discussion Question 3

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3. People as Experimental Units

Example: Cholesterol Drug Study – Suppose we wish to determine whether a drug will help lower the cholesterol level of patients who take it.

How should we design our study?


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Polio Vaccine Example

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Polio Vaccine Example

Dr. Jonas Salk, vaccine pioneer 1914-95

Iron Lung

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The Salk Vaccine Field Trial

• 1954 Public Health Service organized an experiment to test the effectiveness of Salk’s vaccine.

• Need for experiment:– Polio, an epidemic disease with cases

varying considerably from year to year. A drop in polio after vaccination could mean either:• Vaccine effective• No epidemic that year

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Subjects: 2 million, Grades 1, 2, and 3

• 500,000 were vaccinated– (Treatment Group)

• 1 million deliberately not vaccinated– (Control Group)

• 500,000 not vaccinated - parental permission denied

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The Salk Vaccine Field TrialNFIP Design

• Treatment Group: Grade 2

• Control Group: Grades 1 and 3 + No Permission

Flaws ?

• Polio contagious, spreading through contact. i.e. incidence could be greater in Grade 2 (bias against vaccine), or vice-versa.

• Control group included children without parental permission (usually children from lower income families) whereas Treatment group could not (bias against the vaccine).

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The Salk Vaccine Field TrialDouble-Blinded Randomized Controlled Experimental Design• Control group only chosen from those with

parental permission for vaccination• Random assignment to treatment or control

group• Use of placebo (control group given injection of

salted water)• Diagnosticians not told which group the subject

came from (polio can be difficult to diagnose)• i.e., a double-blind randomized controlled

experiment

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(NFIP rate)

(25) Grade 2

(54) Grade 1/3

(44) Grade 2


The double-blind randomized controlled experiment (and NFIP) results

Size ofgroup

Rate per 100,000

Treatment 200,000 28

Control 200,000 71

No consent 350,000 46

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3. People as Experimental Units• control group:

– Receive no treatment or an existing treatment

• blinding: – Subjects don’t know which

treatment they receive• double blind:

– Subjects and administers / diagnosticians are blinded

• placebo: – Inert dummy treatment

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3. People as Experimental Units

• placebo effect:– A common response in humans

when they believe they have been treated.

– Approximately 35% of people respond positively to dummy treatments - the placebo effect

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Observational Studies

• There are two major types of observational studies:

prospective and retrospective studies

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1. Prospective Studies– (looking forward)

– Choose samples now, measure variables and follow up in the future.

– E.g., choose a group of smokers and non-smokers now and observe their health in the future.

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– Looks back at the past.– E.g., a case-control study

• Separate samples for cases and controls (non-cases).

• Look back into the past and compare histories.

• E.g. choose two groups: lung cancer patients and non-lung cancer patients. Compare their smoking histories.

2. Retrospective Studies – (looking back)

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Important Note:

1. Observational studies should use some form of random sampling to obtain representative samples.

2. Observational studies cannot reliably establish causation.

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Controlling for various factors

• A prospective study was carried out over 11 years on a group of smokers and non-smokers showed that there were 7 lung cancer deaths per 100,000 in the non-smoker sample, but 166 lung cancer deaths per 100,000 in the smoker sample.

• This still does not show smoking causes lung cancer because it could be that smokers smoke because of stress and that this stress causes lung cancer.

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Controlling for various factors

• To control for this factor we might divide our samples into different stress categories. We then compare smokers and non-smokers who are in the same stress category.

• This is called controlling for a confounding factor.

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Example 1• “Home births give babies a good chance”

NZ Herald, 1990– An Australian report was stated to have said

that babies are twice as likely to die during or soon after a hospital delivery than those from a home birth.

– The report was based upon simple random samples of home births and hospital births.

Q: Does this mean hospitals are dangerous places to have babies in Australia? Why or why not? Discussion Question 5

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Example 2

• “Lead Exposure Linked to Bad Teeth in Children” ~ USA Today

The study involved 24,901 children ages 2 and older. It showed that the greater the child’s exposure to lead, the more decayed or missing teeth.

Q: Does this show lead exposure causes tooth decay in children? Why or why not?


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Example 2 ~ cont’d

• “Lead Exposure Linked to Bad Teeth in Children” ~ USA Today

Researcher:

“We controlled for income level, the proportion of diet due to carbohydrates, calcium in the diet and the number of days since the last dental visit.”

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Limitations on Scope of Inference

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Discussion Question 7 – Determine Whether Age at 1st Pregnancy is a Risk Factor for Cervical Cancer

How might we proceed?

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Discussion Question 8 – Determine what job related factors Mayo nurses are most dissatisfied with.


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Discussion Question 9 – Determine if a new pre-operative antibiotic reduces the risk of infection for patients undergoing knee replacement.


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Surveys and Polls(and the errors inherent in them)

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NonsamplingErrors

Sampling/Chance/Random Errors

Selection bias Interviewer effects

Non-response bias Behavioural considerations

Self selection Transfer findings

Question effects Survey-format effects

Sampling

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Sources of Nonsampling Errors

Selection bias

Population sampled is not exactly the population of interest.

e.g. KARE 11 poll, telephone interviews

population

sample

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Non-response bias

People who have been targeted to be surveyed do not respond.

Non-respondents tend to behave differently to respondents with respect to the question being asked.

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1936 U.S. Election

• Country struggling to recover from the Great Depression

• 9 million unemployed

• 1929-1933 real income dropped by 1/3

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1936 U.S. Election

• Candidates:

– Albert Landon (Republican)

“The spenders must go!”

– Franklin D Roosevelt (Democrat)Deficit financing - “Balance the budget of the people before balancing the budget of the Nation”

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1936 U.S. Election• Roosevelt’s percentage

–Digest prediction of the election result

–Gallup’s prediction of the Digest prediction

–Gallup’s prediction of the election result

–Actual election result

43%

44%

56%

62%

• Digest sent out 10 million questionnaires to people on club membership lists, telephone directories etc.

– received 2.4 million responses• Gallup Poll used another sample of 50,000• Gallup used a random sample of 3,000 from the Digest lists to predict Digest outcome

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Self-selection bias

People decide themselves whether to be surveyed or not.

Much behavioural research can only use volunteers.

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This poll is not scientific and reflects the opinions of only those Internet users who have chosen to participate. The results cannot be assumed to represent the opinions of Internet users in general, nor the public as a whole. The QuickVote sponsor is not responsible for poll content, functionality or the opinions expressed therein.

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Question effects

Subtle variations in wording can have an effect on responses.

Eg “Should euthanasia be legal?”vs “Should voluntary euthanasia be legal?”

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New York Times/CBS News Poll (8/18/80)

“Do you think there should be an amendment to the constitution prohibiting abortions?”

Yes 29% No 62%

Later the same people were asked:

“Do you think there should be an amendment to the constitution protecting the life of the unborn child?”

Yes 50% No 39%

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Interviewer effects

Different interviewers asking the same question can obtain different results.

Eg sex, race, religion of the interviewer

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Interviewer Effects in Racial Questions

In 1968, one year after a major racial disturbance in Detroit, a sample of black residents were asked:

“Do you personally feel that you trust most white people, some white people or none at all?”

• White interviewer: 35% answered “most”

• Black interviewer: 7% answered “most”

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Behavioural considerationsPeople tend to answer questions in a way they consider to be socially desirable.

e.g. pregnant women being asked about their drinking habits

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Behavioural Considerations in Election

• Official vote counts show that 86.5 million people voted in the 1980 U.S. presidential elections.

• A census bureau survey of 64,000 households some weeks later estimated 93.1 million people voted.

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Transferring findings

Taking the data from one population and transferring the results to another.

e.g. Twin Cities opinions may not be a good indication of opinions in Winona.

Twin Cities sample

Winona

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Survey-format effects

Eg question order, survey layout, interviewed by phone or in- person or mail.

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NonsamplingErrors

Sampling/Chance/Random Errors

Selection bias Interviewer effects

Non-response bias Behavioural considerations

Self selection Transfer findings

Question effects Survey-format effects

Sampling

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SurveyErrors

Sampling/Chance/ Random Errors

NonsamplingErrors

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Sampling / Chance / Random Errors

• errors caused by the act of taking a sample

• have the potential to be bigger in smaller samples than in larger ones

• possible to determine how large they can be

• unavoidable (price of sampling)

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Nonsampling Errors

• can be much larger than sampling errors

• are always present

• can be virtually impossible to correct for after the completion of survey

• virtually impossible to determine how badly they will affect the result

• must try to minimize in design of survey (use a pilot survey etc.)

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Surveys / Polls

A pilot survey is a small survey that is carried out before the main survey and is often used to identify any problems with the survey design (such as potential sources of non-sampling errors).

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Surveys / Polls

A report on a sample survey/poll should include:– target population (population of interest)– sample selection method– the sample size and the margin of error– the date of the survey– the exact question(s)

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