1. QUANTITATIVE EPIDEMIOLOGICAL METHODS AND THEIR APPLICATION IN RESEARCH.
REVISION

2. Overview
Introduction
Quantitative research methods

3. INTRODUCTION Epidemiology
defn:- the study of the distribution and determinants of disease frequency in human populations for the purpose of disease prevention.
Epidemiology is a multi-disciplinary subject.

4. The scope and uses of epidemiology
Description of the distribution of diseases in a population.
Identification of aetiological factors in pathogenesis.
Provide and analyse information for the planning, implementation and evaluation of health services.
Study the natural history of disease.

5. Research
definition:- is the systematic collection, analysis and interpretation of data to answer a certain question or solve a problem. OR
An activity aimed at advancement of knowledge (scientific or non-scientific)

6. Research aims at collection of information that will contribute to the solution of a problem and therefore, provide a basis for action whether immediately or in the long run.

7. Quantitative research methods
Depending on the type of health problem to be investigated a variety of study designs have been developed and grouped into two broad categories. These are observational and experimental studies OR Non-interventional and Interventional studies respectively.

8. Selection of study design
In selecting the design of the study you have to consider the type of information you want to obtain and devise strategies to enable you to obtain that information.
The study design should be appropriate for the study objectives.
The selection of an appropriate research design depends on:-
-state of knowledge about the problem
-the nature of the problem and its environment.
-the resources available for the research

9. the ingenuity and creativity of the researcher.
Depending on the existing state of knowledge of the problem being studied, different types of questions may be asked which require different answers.

10. EPIDEMIOLOGICAL
STUDIES
EXPERIMENTAL
STUDIES
OBSERVATIONAL
STUDIES
Classical design
Randomized control
trials
ANALYTICAL
STUDY
DESCRIPTIVE
STUDY
Clinical trials/
Therapeutic trials
Ecological
Person (who)
Prophylactic trials
Cross-sectional
Place (where)
Case-control
Intervention
trials
Time (when)
Cohort

11. Observational (non-interventional) studies.
These are of three sorts
Exploratory studies.
Descriptive studies.
Analytical (comparative) studies.

12. Exploratory studies.
This is a small scale study of relatively short duration carried out when little is known about a situation or problem. It may include description as well as comparison.
e.g a national acquired immunodefiency syndrome (AIDS) control programme wishes to establish counseling services for HIV positive and AIDS patients, but lacks information on specific needs patients have for support. To explore these needs a number of in depth interviews are held

13. Descriptive studies
These describe pattern of disease occurrence in relation to place, time and person.
These studies are involved with describing the characteristics of a particular situation, event or case.
These studies can be carried out on a small scale or larger scale.

14. 1.Small scale descriptive case studies
Descriptive case studies describe in depth the characteristics of one or a limited number of ‘cases’. A case may be for example, a patient, a health centre, or a village. Such a study can provide quite a useful insight into a problem.

15. 2. Large scale, cross-sectional surveys (prevalence studies).
Cross sectional surveys aims at describing and quantifying the distribution of certain variables in a study population at one point in time.
They can as well be conducted as comparative (analytical) studies.
From a well defined population, disease status and exposure are assessed simultaneously.

16. The point in time could be:
Calendar year (mid year, mid month) or
Fixed point in the course of events which varies in real time form person to person. e.g menarche, adolescence,e.t.c

17. Uses of cross-sectional studies
To determine the magnitude of disease or disease determinants in a community in terms of prevalence.
To study preliminary associations between disease and possible aetiological factors by comparing the characteristics of the sick with those of the healthy.
To screen for undiagnosed disease in a community.

18. Limitations of cross-sectional studies:
Not possible to determine whether the exposure preceded or resulted from the disease. Reflects determinants of survival as well as aetiology.

19. Comparative or analytical studies.
Case-control studies
what is it?
an epidemiologic investigation which involves comparison of characteristics of diseased persons with those of non-diseased persons.
-the purpose is to identify factors which occur more (less) frequently in the cases as compared to the controls and hence provide clues regarding the role of such factors in elevating (reducing) the risk of the disease under investigation.

20. Design and conduct of case control studies
Cases should represent as far as possible a homogenous entity.
Cases should be selected from a well defined population called source population. Possible source of cases could be a hospital/health care facility. Also cases may come from the general population

21. Controls are necessary in order to allow the evaluation of whether the frequency of an exposure or specified characteristic observed in the case group is different from that which would have been expected based on the experience of a series of comparable individuals who do not have the disease. The controls should be selected to represent the population of individuals who would have been identified and included as cases had they also developed the disease.

22. Advantages of case control studies
Efficient in time and cost
Efficient for the study of rare diseases
Efficient for the study of chronic diseases
tends to require a smaller sample sizeas opposed to other designs
allows exploration of a large number of exposure for the disease under investigation.

23. May be completed more rapidly than alternative designs
Ethical problems are minimal
Subjects need to be volunteers.
Attrition problems are minimal
Used to test the hypothesis that the disease in the cases is or is not associated with exposure to some factor hence can provide suggestive evidence of causal relationship that warrants public health intervention to reduce exposure to risk factor

24. Disadvantages of case control studies
Both the exposure and disease have already occurred at the time the participants are recruited into the study, hence the design is susceptible to bias arising from differential selection of cases or controls into the study on the basis of their exposure status as well as from differential reporting or recording of exposure information among study groups based on their disease status
Inefficient in ascertainment of rare exposures.
Temporal relationships usually difficult to ascertain.

25. MEASURE OF EFFECT FROM A CASE CONTROL STUDY.
Results from a case – control study can only provide an estimate of the relative risk (i.e Odds ratio)
This can be done under the assumption that:-
-Controls are representative of the general population with respect to the frequency of exposure.

26. - the assembled cases are representatives of all the cases of the disease
- frequency of the disease in the population is small

27. Odds ratio for unmatched case-control studies
Exposure
status
Disease status
cases
controls
exposed a b
a+b
Not exposed c d
c+d

28. odds ratio= a/c
b/d
=ad/bc

29. Cohort studies
In a cohort study, a group of individuals exposed to a risk factor (study group) is compared to a group of individuals not exposed to a risk factor. (control group)
The researcher follows the groups over time and compares the occurrence of the problem that he expects to be related to the risk factor in the two groups to determine whether a greater proportion of those with the risk factor are indeed affected.

30. Four characteristics of a cohort studies can be identified
-starts with “healthy” subjects who are free of the disease of interest
-Classify them on basis of exposure (risk factor)
-follow subjects and assess the occurrence of outcome of interest among exposure groups
-compare incidence of outcome in both groups

31. Issues for consideration in assembling the cohort
Frequency of the exposure under study
Accessibility of cohort members for measurements and follow up. Incomplete follow up affects validity of the study
Cohort selected should assure sufficient number of outcomes
Selecting a representative of cohort.

32. Advantages of cohort studies
Can elucidate temporal relationship between exposure and disease.
Permits direct measurements of exposure specific incidence of the disease.
Allow for evaluation of multiple outcomes of the same exposure.
Useful for studying rare exposure
Prospective cohort studies are less prone to selection bias.

33. Limitations of cohort studies
Expensive and time consuming and therefore takes long time before completion.
Liable for attrition or loss to follow up among subjects in the study. This can affect validity of the results obtained
Inefficient for rare diseases.
Not suitable for diseases with long latency period as these require long period of follow up.

34. MEASURE OF EFFECT FROM A COHORT STUDY
Data analysis:
Basic analysis of data from a cohort study involves the calculation of rates of the incidence of a specified outcome among the cohorts under investigation.
The basic layout of data at the end of the
study is in the form of a 2x2 table as shown below

35. exposed a b a+b unexposed c d c+d a+c b+d a+b+c+d Not diseased
TOTAL
exposed a b
a+b
unexposed c d
c+d
a+c
b+d
a+b+c+d

36. Cumulative incidence of disease among exposed (Ie)
=a/(a+b)
Cumulative incidence of disease among unexposed (Io)
=c/(c+d)

37. Measure of effect
- Effect of exposure is measured by the ratio Ie/Io, known as Relative Risk (RR).
Relative risk is the measure of strength of the association between exposure and disease. It measures the risk of a disease in exposed group when compared to the unexposed group. A relative risk of 1 shows no increased risk in the exposed group (i.e. no association between exposure and disease); while a RR greater than 1 indicates increased risk among exposed group. A RR of less than 1 indicates a decreased risk in the exposed group.

38. INTERVENTIONAL STUDIES
In intervention studies, the researcher manipulates a situation and measures the effects of this manipulation. Usually (but not always) two groups are compared, one group in which the intervention takes place (e.g treatment with a certain drug) and another group which remain ‘untouched’ (e.g treatment with a placebo)

39. Intervention studies can be:-
experimental studies
quasi-experimental studies

40. Experimental Studies These gives the most reliable proof of causation.
An experiment is a deliberate application or withholding of a supposed cause, and observation for subsequent appearance of an effect.
In an experimental study, individuals are randomly allocated to at least two groups. One group is subject to an intervention, or experiment, while the other group (s) is not. The outcome of the intervention is obtained by comparing the two groups.

41. An experiment on human beings should only be based on removal or addition of a factor which will eventually improve the health of an individual or a community.
In the course of an experiment, an investigator should not cause suffering to anyone in order to prove cause and effect relationship.

42. Types of experimental studies
Classical experiments
Natural experiments
Randomized control trials

43. Classical experimental design
These are carried out on healthy laboratory animals and not on humans because of ethical issues
Typically those involving laboratory animals to test drug toxicity.

44. Natural experiments
These are observations made by comparing two similar populations in which one of them has been exposed to some disease factor as a result of some natural disaster such as famine, earth quakes and wars. The circumstances to exposure and observation for effects have been linked to experiments

45. Randomized control trials
These are studies to determine the efficacy of a drug, vaccine (or any other method of treatment or prevention) in the treatment or prevention of a disease.
Commonest forms of experiments
Randomized control studies are a standard against which all other designs can be compared.
Randomized control studies are comparative with an intervention and a control group.
In these studies, there are known or unknown factors related to disease progress or outcome.

46. Subjects should be assigned to intervention or control group by a way which mostly control for those factors known or unknown so as to produce comparable group other than for intervention.
Comparability between the control groups is achieved by RANDOMIZATION.
This procedure ensures that all individuals have equal probability to be assigned to either control or intervention group.

47. Types of randomized control studies
Therapeutic trials
Interventional studies
Prophylactic trials.

48. Therapeutic trials
These are done to determine the efficacy of a therapeutic agent or a procedure.
There are four phases of therapeutic trials:

49. Phase I
Involves trials which are usually performed on human volunteers.
It is has the following objectives:-
-to understand how much of the drug can be given without causing serious side effects.
-to understand drug metabolism and availabilty
-to determine appropriate dose schedules.
The sample size is usually small involving individuals

50. Phase II Require close monitoring of each patient.
The objectives are:-
-to determine the effectiveness and safety of the drug
-to select drugs with genuine effect from those without beneficial effect or are seriously toxic
The sample size ranges from 100 to 200 patients on each drug.

51. Phase III Done after establishing that the drug is safe and effective.
The drug is compared with the standard treatment for the same condition.
Usually a large trial involving a substantial number of patients.
It is a very vigorous and extensive type of clinical investigation of a new drug.

52. Phase IV
Conducted after the trials in previous phases have established suitability of the drug for marketing.
They are usually large studies and of long term on morbidity and mortality
The major objectives is monitoring for adverse effects of the drug.
It is also an exercise to promote the drug by introducing it to a large number of clinicians.

53. Intervention trials
Intervention is done in those with disease risk factors to reduce the risk for disease

54. Prophylactic trials
Determine the efficacy of prophylactic agents such as vaccines to prevent occurrence of disease

55. RANDOMIZATION
The major reason for doing randomization is to achieve comparability between groups as much as possible.
It produces two or more comparative groups with respect to known and unknown risk factors.
It removes the investigator’s bias in allocating subjects to treatment groups and also guarantees that statistical tests will have valid significance levels.

56. BLINDING In any clinical trial, bias is one of the major concerns.
Bias can occur at a number of places in a clinical trial from the initial design, through data analysis and interpretation. A general solution to the problem of bias is blinding.
Blinding is to keep the subject, observer, or data analyst or all unaware of the assigned intervention.