Post on 02-Jan-2020
Intervention and clinical
epidemiological studies
Including slides from:Barrie M. Margetts
Ian L. Rouse
Mathew J. Reeves,PhD
Dona Schneider
Tage S. Kristensen
Victor J. Schoenbach
Experimental / intervention studies• Experimental studies differ from observational studies described
/reported rather than simply to observe, the exposure of interest.
• There are many different approaches used in experimental studies,
from very tightly controlled laboratory experiments to large scale
community intervention.
• Experimental studies either focus on assessing change at the level of
the individual or the group.
• The most important aspect of experimental studies, no matter what
study group is used., is to ensure that the allocation of the study group
to the different treatments/ interventions / exposures under
investigation is done randomly.
• The development of the research protocol will then focus primarily on
how to measure the effect of an exposure on an outcome with
consideration of the effects of other factors (potential confounders as
well as factors related to the efficacy of the delivery of the intervention)
Effect of psychosocial treatment on
survival of breast cancer patients
Intervention: Group sessions of 90 min. once a week for one
year.
Spiegel et al. Lancet 1989;II:888-91.
0 20 40 60 80 100 120 140
Months from study entry to
death
Probability of survival
0.2
0.4
0.6
0.8
1
0
Holding handsA randomized trial among women giving birth
Support No support
(249) (168)
Perinatal problems 27 % 59 %
Caesarean section 7 % 17 %
Duration of labor 7.7 h 15.5 h
Transferred to neonatal
intensive care2 % 7 %
Support was a ”doula” who stayed with the women during labor and birth.
Klaus et al. BMJ 1986;293:585-7.
Effect of treatment for high blood pressure and
high cholesterol – A randomized trial
Five-year intervention study of 1222 Finnish businessmen
0
10
20
30
40
0 2 4 6 8 10 12 14 16
Years from
randomizationStrandberg et al. JAMA 1991;266:1225-9.
Effects of debriefing after traffic accidents
A randomized trial
Intervention
group *Control group
Median no of days in hospital 7.7 3.7
Emotional distress score 0.50 0.42
Emotional distress after 4 months 0.62 0.38
Mean impact score 15.13 15.30
Mean impact score after 4 months 15.97 12.87
Proportion with distressing memories 21 % 10 %
Number 51 52
* Debriefing for one hour and an information leaflet.
Hobbs et al. BMJ 1996;313:1438-9.
Effect of debriefing ?A study of policemen involved in the Bijlmermeer plane crash disaster
Debriefed Non-debriefed
(N=46) (N=59)
PTSD symptoms, 8 months after 25 % 27 %
Arousal symptoms, 8 months after 6 % 2 %
PTSD symptoms, 18 months after 24 % 17 %
Arousal symptoms, 18 months after 7 % * 0 %
* P < 0.05
Carlier et al. Stress Med 1998;14:143-8.
Relative risk of IHD of workers exposed to
CS2 compared to controls
R
R
Intervention was started in 1972
Nurminen & Hernberg. Br J Industr Med 1985;42:32-5
0
1
2
3
4
5
6
7
8
1967 1972 1977 1982 Calendar year
Follow-up year0 5 10
15
•
•
• •• •
Intervention in details - exampleQ: Does a course in lifting techniques reduce the
occurrence of low back pain ?
1. Did the participants attend the course ?
2. Did the participants learn anything ?
3. Did the participants learn how to do the lifting ?
4. Were the participants able to use the techniques in practice afterwards ?
5. Did the participants use the techniques in practice ?
6. For how long ?
7. Did the use of the new techniques reduce low back pain among those who already had low back pain ?
8. Did the use of the new techniques reduce the incidence of new cases of low back pain ?
Types of Intervention Studies• All trials test the efficacy of an intervention and assess safety
• Prophylactic vs Treatment– evaluate efficacy of intervention designed to preventdisease, e.g., vaccine, vitamin supplement, patient education
– evaluate efficacy of curative drug or intervention or a drug designed to manage signs and symptoms of a disease (e.g., arthritis, hypertension)
• RCT vs Community Trials– individuals, tightly controlled, narrowly focussed, highly select groups, short or long duration
– Cities/regions, less rigidly controlled, long duration, usually primary prevention
Example of a therapeutic trial
The β-Blocker
Heart Attack
Trial (B-HAT)
The β-Blocker Heart Attack trial.
JAMA, Nov. 6, 1981;246(18):2073
Example of a prevention trial
Perinatal
transmission
of HIV
(ACTG 076)
NEJM 11/3/1994;
331(18):1173-1180
• Experimental studies in whole populations (communities) are usually referred to as community trials or community intervention studies.
• Community trials focuses on mass education campaigns aimed at changing people’s knowledge and attitudes.
• Community intervention studies, the exposure is usually given to subjects (for example, by vector control to reduce malaria, pit latrines for clean water), or to reduce work load and/or to increase disposable income.
• These community intervention studies can be characterized as:
(1) explicitly nutritional
(a) nutrition oriented food programs (b) feeding programs
(c) weaning foods (d) fortification (e) nutrition education;
(2) non- or implicitly nutritional
(a) health related, e.g. immunization, sanitation;
(b) economic, e.g. income generation or substitution;
(c) labor-saving, e.g. cereal mills;
(3) integrated
Community trials
Individual trials
• Individual-based experimental studies are sometimes sub-
divided on the basis of the level of the outcome as clinical
trials (or therapeutic, secondary, or tertiary prevention trials),
and field trials (primary prevention trials) where the subjects
do not have any defined level of outcome which may be
classified as disease.
• In addition, a third group of individual-based studies are called
intervention studies, where the individuals who have the
outcome of interest above a certain level at baseline are
excluded. (in a trial of vitamin A supplementation children
with xerophthalmia are excluded).
Types of individual trials
Blinded Not blinded
Randomised Not randomised
Controlled Not controlled
Trial
Why is randomized assignment
of intervention so important?
1. Best assurance that control group (unexposed)
is a valid substitute population
2. Only way to control for unknown factors
3. Facilitates masking of exposure status
4. Avoids ambiguity of time order of exposure
and outcome (most intervention studies
achieve this)
5. Provides foundation for statistical tests –valid quantification of uncertainty
Randomization methods
• Coin toss: subject to bias
• Random number tables or computer program– Computer-generated less subject to bias.
• Should be done by a third party
• For procedure trials where physician not blinded, assignment either done in central call-in center or put in opaque envelopes and revealed to investigator at last possible time.– Prevents investigator from gaming assignment.
20
Single vs. double vs. triple blind?
• Much confusion in use of the terms single, double, and triple blind, hence the study should describe exactly who was blinded.
• Ideally, blinding should occur at all of the following levels:• Patients
• Caregivers
• Data collectors
• Adjudicators of outcomes
• Statisticians
Agree to screening? - Yes Agree to screening? - No
Meet inclusion criteria? - Yes
Wish to continue? - Yes Wish to continue? - No
Agree to randomization? - Yes Agree to randomization? - No
Experimental Population
Validity in experimental trials
Respond to letter? - Yes Respond to letter? - No
Meet inclusion criteria? - No
Are they
similar?
Reference Population
Special forms I.
Crossover Studies
• Subjects begin the study on Treatment A and
later switch to Treatment B
• Patients serve as their own control
• Variation between individuals remains constant
• Washout period between treatments reduces
residual carryover
Design of a Planned Crossover Trial
Randomized
Treatment A
Group 1
Group 1
Group 2
Treatment B
Group 2
Group 2
Group 1
Special forms II.
Factorial Design
• Use the same study population to test
Drug A & Drug B
• Assume:
– The outcomes for each drug are different
– Modes of action are independent
• If you need to terminate the study of Drug
A, you can continue the study to determine
the effects of Drug B instead of beginning
an entirely new study.
Factorial Design for Studying
Effects of Two Treatments
Both A and B
(a)
A only
(b)
B only
(c)
Neither
A nor B
(d)
Treatment B
+ -
+Treatment A
-
Summary of RCTs
• Advantages
– High internal validity
– Able to control selection, confounding and measurement
biases
– True measure of treatment efficacy (cause and effect)
• Disadvantages
– Low external validity (generalizability)
– Strict enrollment criteria creates a unique, highly selected
study population
– Complicated, expensive, time consuming
– Ethical and practical limitations