بسم الله الرحمن الرحيمInterventional studies
Lecture – 8: Interventional studiesInstructional Objectives:At the end of the lecture, the students would be able to:1-To identify the design of the Randomized Controlled Clinical Trial RCCT, and their advantages and disadvantages. 2- To be able to a- draw a diagram of main design of RCCT.b- classify the experimental group and the control group.c- demonstrate the effect of volunteer, randomization, compliance and non -compliance, placebo in the RCCT.
This type of study is similar to cohort studies, but the difference is that the investigator themselves will allocate the exposure i.e.Individuals are included on the basis of exposure, but the investigators allocate the exposure . Two types 1-Randomized Controlled Clinical Trial (RCT): Individuals similar at the beginning are randomly allocated and exposed to a treatment group and a control group. The outcomes of the groups are compared after sufficient follow-up time. Properly executed, the RCT is the strongest evidence of the clinical efficacy of preventive and therapeutic procedures in the clinical setting. 2- Community trials : Communities instead of individuals are allocated and exposed to an experiment. The experimental group a community exposed to an experimental factor and the control a group a community that is not exposed to the experimental factor. The results are compared.
Randomized Controlled Clinical Trial (RCCT)
Two groups are selected: The 1st is the experimental group. The subjects are exposed to a factor as an experiment under medical supervision. The 2nd is the control group. The subjects are not exposed to that factor. These two groups are selected on random basis. Random selection means: every subject in the sample has the an equal chance to be chosen in the experimental group or in the control group. The main difference between experimental and analytic cohort studies, is that the investigator in the experimental studies, allocates by himself the study groups into: experimental group and the control group. While in the analytic cohort studies the participants are naturally allocated into exposed and non exposed.Strengths or advantages :-
1.It is regarded as the gold standard of the epidemiological studies. It is the strongest & the most direct epidemiology evidence to judge the causal association . " like an experiment in the lab where the exposure is under the investigators control , who controls all the factors except the risk factor ".2.It can detect mild to moderate difference (10-20%) which is difficult in cohort studies . e.g. conducting a study on which medication should be given after a myocardial infarction MI, should it be B-blockers or Ca++ channel blockers for the prognosis of MI ? Here the difference will be very small (2-5%) but very important to find it out to save patients lives .
3.It can control & manipulate many confounders . 4.It can demonstrate the temporal relationship between the exposure & outcome with the highest degree of confidence .
Limitations or disadvantages :-
1.Expensive & time consuming 2.It doesn't represent the real life situation " because we control all the other factors except the exposure . 3.Ethical problems : for certain factors , there is some doubt about the benefit or harm to the study subject. 4.Feasibility problems: were it is difficult to find the control" non exposed: group. e.g. a study in a city about Vitamin C supplement & disease , here it was hard to find a control group because the majority of the population used vitamin C supplement .The participants should be informed about : The aim of the study, possible benefits, side effects & the possibility of having a placebo during the study period .
A diagram of conducting the study
Screening for eligibility ( inclusion & exclusion )
accepting & eligible
Randomization into: Rx ( exposure group ) : Control group Compare
Study population randomization Sampling
Causes of exclusion :- 1.Definite history of out come under study. 2.Definite need for the study treatment " like someone has Diabetes Mellitus we must give him a treatment & not placebo. 3.Contraindication to the study treatment. e.g. giving aspirin to someone with peptic ulcer.
Volunteer Baias: The volunteers do not represent the true community population on which we will generalize the study result " because not everyone will accept to participate in the study".
Randomization Allocation of the individuals to be included in the exposure status is random, that is to say every individuals is given an equal chance to be allocated in the exposure or non- exposure groups .
NOTE : The measure of association between disease & exposure is the relative risk attributable risk and attributable risk % as in cohort study .
Maintenance of Assessment of compliance :Compliance : the commitment of the study participants by the treatment التزام المشارك. The non- compliance is the major problem in the intervention. it's related to the complexity & the length of the follow-up .
Causes of non -compliance : ( non –compliance decrease as the statistical power of the study is decreased )1.development of side effects .2.forgetting to take the treatment. 3.withdrawal from trials. 4.choosing the alternative method. 5.the intervention becomes contraindicated Enhancement of compliance is by :1. inclusion of interested & reliable groups 2.frequent contact with participants3. use of calendar pack of study treatment as in contraceptive pills each pill has a date on it .4. provision of incentives " حوافز “either financial or medical insurance “
Placebo: A placebo is the non treatment material used in a control group in place of the actual treatment. If a drug is being evaluated, the inactive vehicle or carrier is used alone so it is as similar as possible in appearance and in administration to the active drug. Placebos are used to blind observers and, for human trials, the patients to which group the patient is allocated. Limitation of placebo : 1.There is a tendency of the patient to report a good result of any treatment. 2.tendency to report side effects with the Rx or placebo
Sampling A sample is a group of individuals that is a subset of a population and has been selected from the population in some fashion (random or haphazard). Types : 1.Simple Random Sampling / Allocation: Require a complete list of identified individuals making up the population (the list frame) before the sampling can be done. Choose haphazardly the size of participants is small. e.g. 10 of 30 no. 2.Systematic Sampling: From a random start in first n individuals, sampling every nth animal as they are presented at the sampling site (clinic, chute, ...). Systematic sampling will not produce a random sample if a cyclical pattern is present in the important characteristics of the individuals as they are presented
3.Stratified Random Sampling: The group from which the sample is to be taken is first stratified on the basis of a important characteristic related to the problem at hand (e.g., age, parity, weight) into subgroups such that each individual in a subgroup has the same probability of being included in the sample but the probabilities are different between the subgroups or strata. Stratified random sampling assures that the different categories of the characteristic that is the basis of the strata are sufficiently represented in the sample . 4.Cluster Sampling: Staged sampling in which a random sample of natural groupings of individuals (houses, households) are selected and then sampling all the individuals within the cluster. Cluster sampling requires special statistical methods for proper analysis of the data and is not advantageous if the individuals are highly correlated within a group (a strong herd effect).