EXPERIMENTAL EPIDEMIOLOGY

THIS PRESENTATION TAKEN PARK BOOK OF SPM &AFMC BOOK.

1. EXPERIMENTAL EPIDEMIOLOGY DR m a thaher Pg 1 st year COMMUNITY MEDICINE 07/04/2015

2. “THE SMOKING OF 30-40 CIGARETTS PER DAY CAUSES LUNG CANCER IN 10% OFSMOKERS AFTER 20 YEARS OF EXPOSURE” HYPOTHESIS

3. EPIDEMIOLOGY METHODS 1.OBSERVATIONAL STUDIES A.DESCRIPTIVE B.ANALYTICAL STUDIES STUDIES 1.ECOLOGICAL 2.CROSS- SECTIONAL 3CASE-CONTROL 4.COHORT HYPOTHESIS FORMULATION TESTING 2.EXPERIMENTAL STUDIES INTERVENTIONAL STU A. RCT B.FIELD TRIALS C.COMMUNITY TRIALS CONFORMATION

4. EXPERIMENTAL EPIDEMIOLOGY In the 1920s,”experimental epidemiology” meant the study of epidemics among colonies of experimental animals such as rats and mice.in modern usage,experimental epidemiology is often equated with RCT. AIMS To provide a scientific proof. To provide a measuring method.

5. Animal studies At the beginning of this century ,,WEBSTER(us) andTOPLEY,WILSONand GREENWOOD( england ) carried out animal experiments. ADVANTAGES Experimental animals can be bred inlab,manpulated easily according to investigator wishes. Multyply rapidly

6. Limitations:- Not all the diseases reproduse in animals. All the conclusions derived from animal experiments may not be strictly appicable to human beings. EX:-WHO trial on typoid vaccine.-Almorth Wright RCT trials. Animal studies

7. HUMAN EXPERIMENTS Human experiments will always be needed to investigate disease aetiology and to evaluate the preventive and therapeutic measures. These studies are even more essential in the investigation of diseases that cannot be reproduced in animals. Ex: JAMES LIND EDWARD JENNER GOLDBERGER’S EXPERIMENT.

8. Although the experimental method is unquestionably the most incisive approach to scientific problem, ethical and Iogistic considerations often prevent its application to the study of disease in humans. Therefore, before launching human experiments, the benefits of the experiment have to be weighed against risks involved. The volunteers should be made fully aware of all possible consequences of the EXPERIMENT. Thus when an illness is fatal (e.g., excessive haemorrhage ) and the benefit of treatment (e.g., blood transfusion) is self-evident, it would be ethically unacceptable to prove or disprove the therapeutic value of blood.

9. However, such instances represent only a small part of the total research effort. On the other hand, in the present era of scientific medicine, many unscientific or scientifically unsound procedures are still being carried out. EX;diethylstilbesteral-ca.vagina . The WHO in 1980 has laid down a strict code of practice in connection with human trials. Experimental studies are two types. A. RCT B. NON-RANDAMOISED.

10. It IS really an epidemiologic experiment. Since its introduction. The RCT has questioned the validity of such widely used treatments as oral hypoglycemic agents, varicose vein stripping, tonsillectomy, ……etc For new programmes or new therapies, the RCT is the No.1 method of evaluation. RANDOMIZED CONTROL TRIALS

11. Basic steps in RCT conducting: 1.Drawing up a protocol. 2.Selecting reference and experimental populations. 3.Randomization . 4.Manipulation or intervention 5.Follow –up 6.Assessment of outcome

12. It specifies:- Aims &objectives of study Questions to be answered Criteria for selection of study and control groups Size of sample The procedures for allocation of subjects into study and control groups. Treatment to be applied. Standardization of working procedures Schedules and responsibilities of the parties involved 1.The protocol

13. AIM:- preventing bias and to reduce the source of errors in the study. Preliminary test runs : some times it is useful to have short test to run of the protocol to see any flaws Protocol

14. REFERANCE POPULATION :- Population to which the findings of the trail are expected to be applicable. Ex :-specific age group people geographically limited population of school children SELECTING REFERENCE &EXPERIMENTAL POPULATION

15. it is derived from reference population. It is the population that actully participates in experimental studies. Participants must fullfil 3 criterias …. 1.must give informed consent 2.should be representative of the population. 3.should be eligible for the trail. EXPERIMENTAL POPULATION

16. it is a statistical procedure by which participents allocated in to study and control groups. it is a heart of RCT It is an attempt to eliminate bias and allow for comparability. It will give greatest confidence that the groups are comparable so that”like can be compared with like”. RANDOMIZATION

17. Randomization is done only after the participants entered the study,that is after having been qualified for the trial and has given informed consent to participate in study. Randomization best done by using a table of random numbers.(simple random sample).random numbers are a haphazard collection of certain numbers,arranged in a cunning manner to eliminate personal selection of unconscious bias in taking out the sample. Randomization

18. After selection of study& control group,intervene the study group by deliberate application(vaccine , drug ) as laid down in protocol. This manipulation creates an independen t varieble ( e.g . drug,vaccine )whose effect is then determined by measurement of the final outcome,which constitutes the dependen t varieble (incidence of disease,survival time.) MANIPULATION

19. This implies examination of the experimental & control group subjects at defined intervals of time,in a standard manner,with equal intensity,under the same given circumstances,in the same time frame till final assessment of outcome. Attrition:- some cases losses to follow-up due to death,migration,loss of intrest . If the attrition is substantial,it may be difficult to generalise the results to refferens population. FOLLOW-UP

20. POSITIVE RESULTS:- Benefits of experiment measurers reduced incidence or severity of disease….. NEGATIVE RESULTS:- Severity and frequency of side-effects and complications,if any,including death. ASSESSMENT

21. Bias may arise from errors of assessment of the outcome due to human element.these may be from 3 sourses . First - bias from the participants,who may subjectively feel better or report improvement if they knew they were receiving a new form of treatment.known as subjective variation. Second – investigater measuring the outcome of a trial may be influnced if he knows beforehand the particular therapy to which the pt has subjected.( observer variation) BIAS

22. BLINDING:- In order to reduce above problems,blinding is adapted .it can be done in 3 ways. A. Single blind trials:-participant is not aware of group allocation. B. Double blind trials:-neither doctor nor participant is aware of group allocation.& Rx received. C. Triple blind trials:-participant,investigater and person analysing data are blind. Third there may be bias in evaluation.-the investigator may give subconsciously give a favorable report of the outcome of trial .

23. 1.Concurrent parallel study designs 2.Cross over type of study design. STUDY DESIGNS

24. Concurrent parallal study designs.

25. Cross over type of study design

26. For the most part,”clinical trials” have been concerned with evaluting therapeutic agents,mainly drugs. Eg : trials of folate - to prevent NTD. efficacy of tronsillectomy for recurrent throat infections . M any ethical, administrative, & technical problems are involved in the conduct of clinical trials. Types of RCT- 1.clinical trials

27. I t implies primary prevention. M ost common trials are done vaccines & chemoprophilactic Eg : Medical research concil of UK – woophing cough since preventive trials involve larger number of subjects and longer time span to obtain results,there may be greater number of practical problems in their organisation and execution. 2.Preventive trials

28. A type of prevenive trials in which he investigator internvenes to interrupt the usual sequence in the development of disease for those individual who has risk factor in developing the disease Often this involves risk factor modification Eg . CHD- 4 major risk factor- WHO study- clofibrate therapy OSLO study, MRFIT in US 3.Risk factor trial

29. Another type of preventive trial is ihe cessation experiment. In this type of study, an attempt is made to evaluate the termination of a habit (or removal of suspectedagent ) which is considered to be causally related to a disease. If such action is followed by a significant reduction in the disease, the hypothesis of cause is greatly strengthened. Ex :cigarette smoking-lung cancer. Cessetion experiments

30. One of the aim of experimental etiology is to confirm or refute etiological hypothesis . eg ;: RLF Since most disease are fatal,disabling , human experiments to conform an aetiological hypothesis are rarely possible. 5. Trial of etiological agents

31. RCT have been extended to assess the efectiveness & efficiency of health services. Eg : Domicilliary treatment- pulm . Tuberculosis. Health services research studies. 6.Evaluaton of health services

32. Due to ethical, administrative, cost it is not always possible to resort to RCT. Approach is crude. As there is no randamisation , degree of comparability will be low and chances of spurious results will be high. Non Randamized Trials

33. 1. Uncontrolled trials : Trials with no comparision groups. Useful to known whether specific therapy is valuable for particular disease, to determine the appropriate dose, to investigate adverse reaction. Eg:indirect epidemiological evidence that the pap test is effective in reducing mortality from cervical cancer. Examples of non randamized trials

34. 2. Natural experiments: Where experimental studies are not possible in human beings, some natural circumstances mimics as experiment Eg : smokers and non smokers- lung cancer. John snow discovery- cholera- water born disease. Non-randomized trials

35. John snow’s experiment

36. 3.BEFORE AND AFTER COMPARISON STUDIES: These community trials fall into 2 distinct groups. A.Before & after comparison studies without control. B.Before & after comparison studies wth control Non-Randomized trials

37. These studies centre round comparing the incidence ofdisease before and after introduction of a preventive measure. The events which took place prior to the use of the new treatment or preventive procedure are used as a standard for comparison. In other words, the experiment serves as its own control; this eliminates virtually all group differences. Before &after comparison studies without control

38. Ex:James Lind – scury experiment Prevention of polio by salk and sabin vaccine In order to establish evidence in before and after comparison studies, the following are needed; (a) data regarding the incidence of disease, before and after introduction of a preventive measure must be available (b) there should be introduction or manipulation of only one factor or change relevant to the situation, other factors remaining the same. as for example, addition of fluorine to drinking water to prevent dental caries (c) diagnostic criteria of the disease should remain the same (d) adoption of preventive measures should be over a wide area (e) reduction in the incidence must be large following the introduction of the preventive measure, because there is no control.

39. 1970 1971 %change deaths 564 464 -17.7 injuries 14620 12454 -14.8 Effect ofadoption of compulsory seat-belt legislation in vectoria,Aus-1971

40. In the absence of a control group, comparison between observations before and after the use of a new treatment or procedure may be misleading. In such situations, the epidemiologist tries to utilize a "natural" control group i.e., the one provided by nature or natural circumstances. If the preventive programme is to be applied to an entire community. he would select another community as similar as possible, particularly with respect to frequency and characteristics of the disease to be prevented. Before and after comparison studies with control

41. 1970 1971 %change DEATHS Victoria 564 464 -17.7 Other states 1426 1429 0.2 INJURIES Victoria 14620 12,454 -14.8 Other states 39,980 40,396 1.0 Effect of adaptation of compulsary seat-belt legislation in victoria comparing with other states(where legislation not applied)

42. Scientifically ideal method. Removes a large number of biases related to selection and measurement, Ensures temporal relationship between exposure and outcome. Builds up ‘faith ‘ in the findings of the study. A dvantages

43. In many situations, rspecially those which concern study of risk factors or prognostic factors,one can not randomly allocate human beings into two groups. Eg ;-smoking- lung cancer Ethical issues. Expensive Long time need….. Disadvantages

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