Intervention and clinical epidemiological studies

Transcription

1 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

2 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)

3 Intervention is not always successful see following examples carefully!

4 Effect of psychosocial treatment on survival of breast cancer patients Probability of survival Intervention: Group sessions of 90 min. once a week for one 1year Months from study entry to death Spiegel et al. Lancet 1989;II:

5 Holding hands A 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 care 2 % 7 % Support was a doula who stayed with the women during labor and birth. Klaus et al. BMJ 1986;293:585-7.

6 Effect of treatment for high blood pressure and high cholesterol A randomized trial Five-year intervention study of 1222 Finnish businessmen Years from Strandberg et al. JAMA 1991;266: randomization

7 Effects of debriefing after traffic accidents A randomized trial Intervention group * Control group Median no of days in hospital Emotional distress score Emotional distress after 4 months Mean impact score Mean impact score after 4 months Proportion with distressing memories 21 % 10 % Number * Debriefing for one hour and an information leaflet. Hobbs et al. BMJ 1996;313:

8 Effect of debriefing? A study of policemen involved in the Bijlmermeer plane crash disaster Debriefed (N=46) Non-debriefed (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.

9 Relative risk of IHD of workers exposed to CS 2 compared to controls R R Intervention was started in Calendar year Nurminen 15& Hernberg. Br J Industr Med 1985;42:32-5 Follow-up year

10 Intervention in details - example Q: 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?

11 Types of Intervention Studies All trials test the efficacy of an intervention and assess safety Prophylactic vs Treatment evaluate efficacy of intervention designed to prevent disease, 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

12 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

13 Example of a prevention trial Perinatal transmission of HIV (ACTG 076) NEJM 11/3/1994; 331(18):

14 Community trials 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

15 Individual trials Individual-based experimental studies are sometimes subdivided 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).

16 Types of individual trials Trial Controlled Not controlled Randomised Not randomised Blinded Not blinded

17 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

18 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.

19 Randomised clinical trials

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 20

21 Double blind trials

22 Validity in experimental trials Reference Population Respond to letter? - Yes Agree to screening? - Yes Meet inclusion criteria? - Yes Wish to continue? - Yes Agree to randomization? - Yes Respond to letter? - No Agree to screening? - No Meet inclusion criteria? - No Wish to continue? - No Agree to randomization? - No Are they similar? Experimental Population

23 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

24 Design of a Planned Crossover Trial Randomized Treatment A Treatment B Group 1 Group 2 Group 1 Group 2 Group 2 Group 1

25 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.

26 Factorial Design for Studying Effects of Two Treatments Treatment B + - Treatment A + Both A and B (a) A only (b) Neither - B only (c) A nor B (d)

27 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