Advancing Health Through Experimental Epidemiology: Randomized Control Trails

1. Experimental epidemiology; Randomized Control Trail Dr. Asif Rehman

2. Experimental epidemiology; Randomized Control Trail Aim of experimental studies: • To provide scientific proof of etiological factors which may permit the modification or control of those disease. • To provide a method of measuring the effectiveness and efficiency of health services for the prevention, control and treatment of disease and improve the health of the community.

3. Experimental epidemiology; Randomized Control Trail Randomized Control Trail (RCT): • In 1747, James Lind performed a human experiment (clinical trail) in which he added different substances to diet of 12 soldiers who were suffering from Scurvy. He divided his patient in to 6 pairs and supplemented the diets of each pairs with cider, elixir vitriol(aromatic Sulphuric acid), vinegar, sea water, a mixture of nutmeg, garlic, mustard and tamarind (Indian dates) and two oranges and one lemon. All the subjects were studied for 6 days, at the end of 6 days the LIMEYS recovered from Scurvy and found fit for duty.

4. Experimental epidemiology; Randomized Control Trail Randomized Control Trail (RCT): • Experimental or intervention studies are similar in approach to cohort studies excepting that the conditions in which the study is carried out are under the direct control of the investigator. • It involves some action, intervention or manipulation such as deliberate application or withdrawal of a suspected cause or changing one variable in the causative chain in the experiment group while making no change in the control group and observing and comparing the outcome of the experiment in both the group.

5. Experimental epidemiology; Randomized Control Trail Selected Suitable Population Make Necessary Exclusion Randomized (Experimental Group) (Control Group) Manipulation & Follow-up Assessment

6. Experimental epidemiology; Randomized Control Trail Randomized control trail; The basic steps in conducting a RCT includes the following; • Drawing up a protocol. • Selecting reference and experimental populations. • Randomization. • Manipulation or intervention. • Follow up. • Assessment of outcome.

7. Experimental epidemiology; Randomized Control Trail Randomized control trail; 1) Drawing up a protocol; One of the essential features of RCT is that the study is conducted under a strict protocol. The protocol aims at preventing bias and to reduce the source of error in the study. It specifies the aims and objectives of the study, questions to be answered, criteria for the selection of study and control group, sample size, the procedure for the allocation of subjects into the study and control group, treatment to be applied etc.

8. Experimental epidemiology; Randomized Control Trail Randomized control trail; 2) Selecting reference & experimental populations; Ideally it should be randomly chosen from the reference population so that it has the same characteristics as the reference population. If it differs it may not be possible to generalized the findings of the study to the reference population. The participants must fulfill the following criteria: • They must give informed consent • They should be the representative of the population to which they belong. • They should be qualified or eligible for the study.

9. Experimental epidemiology; Randomized Control Trail Randomized control trail; 3) Randomization; It is a statistical procedure by which the participants are allocated into groups usually called study and control group to receive or not to receive an experimental intervention. It ensures that the investigator has no control over allocation of participants to either study or control group thus eliminating “selection bias”. By random allocation, every individual gets an equal chance of being allocated into either group. Randomization is done only after the participant has entered the study, that is after having being qualified and has given informed consent.

10. Experimental epidemiology; Randomized Control Trail Randomized control trail; 4) Manipulation or intervention; Having formed the study and control groups, the next step is to intervene or manipulate the study group by the deliberate application or withdrawal or reduction of the suspected causal factor. (e.g this may be a drug, vaccine dietary component, a habit etc.) as laid down in protocol. This manipulation creates an independent variable e.g. drug, vaccine whose effect is then determined by measurement of the final outcome, which constitutes the dependent variable e.g. incidence of disease, survival time, recovery time.

11. Experimental epidemiology; Randomized Control Trail Randomized control trail; 4) Follow-up; This implies examination of the experimental and control group subjects at defined interval of time, in a standard manner, with equal intensity, under the same given circumstances, in the same time frame till final assessment of outcome. The duration of the trail is usually based on the expectation that a significant difference (mortality) will be demonstrable at a given point in time after the start of the trail. Some losses to follow up are inevitable due to factors such as death, migration and loss of interest. This is known as attrition.

12. Experimental epidemiology; Randomized Control Trail Randomized control trail; 4) Assessment of outcome; The final step is assessment of the outcome of the trail in terms of Positive health; that is benefits of the experimental measure such as reduced incidence or severity of the disease, cost to the health services or other appropriate outcome in the study and control group. Negative results; that is, severity and frequency of side effects and complication, if any, including death. The incidence of positive/negative results is rigorously compared in both groups, and the differences, if any, are tested for statistical significances.

13. Experimental epidemiology; Randomized Control Trail Bias; Any systematic error that results in an incorrect estimation of the association b/w an exposure and the outcome is called bias. This may be from three sources; Subject variations;There may be bias on the part of the participants, who may report improvement if they knew they receiving a new form of treatment. Observer bias;The investigator measuring the outcome of the trail may be influenced if he knows beforehand the particular procedure. Evaluation bias;The investigator may subconsciously may give a favorable report of the outcome of the trail. In order to reduce these problems, a technique known as Blinding is adopted.

14. Experimental epidemiology; Randomized Control Trail Blinding; Blinding can be done in three ways; • Single blind trail;The trail is so planned that the participant is not aware whether he belongs to the study or control group. • Double blind trail;The trail is so planned that neither the researcher nor the participant is aware of the group allocation & the treatment received. • Triple blind trail;This goes one step further. The participant , the investigator and the person analyzing the data are all blind. ideally the triple blind should be used but the double blinding is the most frequently used method when a blind trail is conducted.

15. Experimental epidemiology; Randomized Control Trail Some study design of controlled trail; • Concurrent parallel study design; comparisons are made b/w two randomly assigned groups, one exposed to specific treatment and the other group not exposed. Patients remains in the study group or the control group for the duration of the investigation. Observation Exposed to Rx Patients Outcome Not exposed to Rx

16. Experimental epidemiology; Randomized Control Trail 2) Cross-Over type; In this design, each patient serves as his own control. As before, the patient are randomly assigned to a study group and control group. The study group receives the Rx under consideration. The control group receives placebo. The 2groups are observed over time. Then patients in each group are taken off their medications or placebo to allow for elimination of the medication from the body &for the possibility of any carry over effects by the diagonal lines. After this period of medication the two groups are switched. Those who received the treatment under study are changed to the control group therapy or placebo and vice versa. Observation Exposed to Rx Patients Outcome Not exposed to Rx

17. Identify study design ? • Resident of three villages with three different types of water supply were asked to participate in a survey to identify cholera carriers. Because several cholera deaths had occurred recently, virtually everyone present at the time underwent examination. The proportion of residents in each village who were carriers was computed and compared. What is the proper classification for this study?

18. Identify study design ? • In a small pilot study, 12 women with endometrial cancer and 12 women with no apparent diseases were contacted and asked whether they had ever used estrogen. Each women with cancer was matched by age, race, weight and parity to a women without disease. What is the proper classification for this study?

19. Identify study design? • In a study begun in 1965, a group of 3,000 adults were asked about cigarette smoking. The occurrence of case of cancer between 1981 and 1995 was studied in this group. What is the proper classification for this study?

20. Identify study design? A clinical trial is set up to compare a proposed new drug with a placebo (some inert substance that is given to make people think they are talking a drug when they are not). 50 patients are recruited, and we randomly select 25 of them to receive the new drug, the rest receiving the placebo. After some period of time the two groups are compared to see whether the group receiving the new drug has recovered from the disease under study.

21. THANK YOU