Types of studies in research

research methodology in medicine

1. Types of Studies in Research Dr Yashodhara Gaur Professor, G.R. Medical College, Gwalior President Obst Gynaecology Society Gwalior

2. Research Study Statistical inference Biological inference Study sample Conclusion about a population (association) Conclusion about scientific theory(causation)

3. Observational study designs Experimental study Descriptive studies (Interventional study) Case reports Clinical trials Case series Analytical study designs Retrospective studies Case control study Prospective study designs Cohort study Type of Research Studies

4. ____________________________________________________________________ Observational studies Interventional studies ____________________________________________________________________ Cross-sectional Case-control Cohort Clinical trials Outcome Yes Yes No No Exposure Yes Yes Yes Yes Time of enquiry Still (one time contact) _______________________________________________________________________ _______ Objective Descriptive Analytical studies Burden of problem Causal relationship Hypothesis generation Hypothesis generation & testing Research Studies Eye-catching Point

5. Case Control Study

6. Case Control Study A case-control study is designed to help determine if an exposure is associated with an outcome (i.e., disease or condition of interest) In theory, the case-control study can be described simply. First, identify the cases (a group known to have the outcome) and the controls (a group known to be free of the outcome) Then, look back in time to learn which subjects in each group had the exposure(s), comparing the frequency of the exposure in the case group to the control group. By definition, a case-control study is always retrospective because it starts with an outcome then traces back to investigate exposures

7. Case Control Study Both exposure and outcome(disease) have occurred before the start of study The study proceeds backwards from effect to cause, and is thus called retrospective It uses a control or comparison group to support or refute an inference

8. Case Control: Study Design

9. Venous thromboembolism Without venous present (cases) thromboembolism (controls) Oral contraceptive Exposure present a b Not exposed c d Odds of disease in the exposed group: a/b Odds of disease in the unexposed group: c/d Odds Ratio= (a/b)/(c/d)=ad/ bc Case Control Study (Example)

10. Case control study Applications in research: Particularly appropriate for Investigating outbreaks: Study of endophthalmitis following ocular surgery. When an outbreak is in progress, answers must be obtained quickly Studying rare diseases or outcomes: Study of risk factors for uveal melanoma, or corneal ulcers

11. Steps in conducting a Case-control study Define a study population (source of cases and controls) Define and select cases Define and select controls Measure exposure Estimate disease risk associated with exposure

12. Case Control Study Advantage & Disadvantage Advantages Can obtain findings quickly Can often be undertaken with minimal funding Efficient for rare diseases Can study multiple exposures Generally requires few study subjects Disadvantages Cannot generate incidence data Subject to bias Difficult if record keeping is either inadequate or unreliable Selection of controls can be difficult

13. Cohort Study

14. Cohort Study Group of people with defined characteristics who are followed up to determine incidence of, or mortality from, some specific disease, all causes of death, or some other outcome.” In a cohort study, an outcome or disease-free study population is first identified by the exposure or event of interest and followed in time until the disease or outcome of interest occurs Because exposure is identified before the outcome, cohort studies have a temporal framework to assess causality and thus have the potential to provide the strongest scientific evidence

15. Cohort Study: Design

16. Cohort Study Cohort studies are particularly advantageous for examining rare exposures because subjects are selected by their exposure status Additionally, the investigator can examine multiple outcomes simultaneously.

17. Five steps in a cohort study Identify the study subjects; i.e. the cohort population. Obtain baseline data on the exposure; measure the exposure at the start. (The exposure may be a particular event, a permanent state or a reversible state.)   Select a sub-classification of the cohort—the unexposed control cohort—to be the comparison group.

18. Five steps in a cohort study Follow up; measure the outcomes using records, interviews or examinations. (Note: Outcomes must be defined in advance and should be specific and measurable.) Do the data analysis where the outcomes are assessed and compared.

19. Cohort studies: Types Prospective or Retrospective Prospective studies are carried out from the present time into the future Because prospective studies are designed with specific data collection methods, it has the advantage of being tailored to collect specific exposure data and may be more complete The disadvantage of a prospective cohort study may be the long follow-up period while waiting for events or diseases to occur Thus, this study design is inefficient for investigating diseases with long latency periods and is vulnerable to a high loss to follow-up rate

20. Cohort studies: Types Prospective or Retrospective Retrospective cohort studies, also known as historical cohort studies, are carried out at the present time and look to the past to examine medical events or outcomes In other words, a cohort of subjects selected based on exposure status is chosen at the present time, and outcome data (i.e. disease status, event status), which was measured in the past, are reconstructed for analysis The primary disadvantage of this study design is the limited control the investigator has over data collection The existing data may be incomplete, inaccurate, or inconsistently measured between subjects However, because of the immediate availability of the data, this study design is comparatively less costly and shorter than prospective cohort studies.

21. Cohort Study: Advantages Gather data regarding sequence of events; can assess causality Examine multiple outcomes for a given exposure Good for investigating rare exposures Can calculate rates of disease in exposed and unexposed individuals over time (e.g. incidence, relative risk)

22. Cohort Study: Disadvantages Large numbers of subjects are required to study rare exposures Susceptible to selection bias Prospective Cohort Study May be expensive to conduct May require long durations for follow-up Maintaining follow-up may be difficult Susceptible to loss to follow-up or withdrawals Retrospective Cohort Study Susceptible to recall bias or information bias Less control over variables

23. Snapshot Temporal Design of Observational Studies

24. STROBE stands for an international, collaborative initiative of epidemiologists, methodologists, statisticians, researchers and journal editors involved in the conduct and dissemination of observational studies, with the common aim of STrengthening the Reporting of OBservational studies in Epidemiology . The STROBE Statement is being endorsed by a growing number of biomedical journals https://www.strobe-statement.org/index.php?id=available-checklists

25. Cross-sectional Study

26. Cross-sectional Study Cross-sectional study design is a type of observational study design In a cross-sectional study, the investigator measures the outcome and the exposures in the study participants at the same time The investigator can study the association between these variables It is also possible that the investigator will recruit the study participants and examine the outcomes in this population The investigator may also estimate the prevalence of the outcome in those surveyed

27. Cross-sectional study Participants recruited based on inclusion and exclusion criteria Estimate the prevalence (of exposure and outcome as well) Calculate odds ratio Study the exposure and outcome at the same time

28. Measurements in a Cross-sectional Study Cross-sectional study designs may be used for population-based surveys Cross-sectional studies may also be used for estimating the prevalence in clinic-based studies. (What is the prevalence of HIV in patients presenting with an STI?) Cross-sectional studies may also be used to calculate the Odd-ratios

29. Strengths of a Cross-sectional Study Cross-sectional studies can usually be conducted relatively faster and are inexpensive – particularly when compared with cohort studies (prospective) These are studies are conducted either before planning a cohort study or a baseline in a cohort study. These types of designs will give us information about the prevalence of outcomes or exposures; this information will be useful for designing the cohort study These study designs may be useful for public health planning, monitoring, and evaluation. For example, sometimes the National AIDS Programme conducted cross-sectional sentinel surveys among high-risk groups and ante-natal mothers every year to monitor the prevalence of HIV in these groups.

30. Limitations of a Cross-sectional Study Since this is a 1-time measurement of exposure and outcome, it is difficult to derive causal relationships from cross-sectional analysis Careful about interpreting the associations and direction of associations from a cross-sectional survey Prevalence of an outcome depends on the incidence of the disease as well as the length of survival following the outcome

31. Case reports and Case series

32. Case reports and Case series Case reports , which generally consist of three or fewer patients, are prepared to illustrate features in the practice of medicine and potentially create new research questions that may contribute to the acquisition of additional knowledge in the literature Case series involve multiple patients; they are a qualitative research method and include in-depth analyses or experiential inquiries of a person or group in their real-world setting

33. Case reports and Case series Applications Clinical case reports and case series are beneficial tools in graduate medical education The preparation and presentation of case studies can help students and residents acquire and apply clinical competencies in the areas of medical knowledge, practice-based learning, systems-based practice, professionalism, and communication In this aspect, case studies provide a tool for developing clinical skills through problem-based learning methods Descriptive studies that are prepared for illustrating novel, unusual, or atypical features identified in patients in medical practice, and they potentially generate new research questions

34. Advantages of Case reports & Case studies One case to initiate a signal (case report) Provide stronger evidence with multiple cases (cases series) Observational Educational Easy to do (fast and no financial support needed) Identify rare manifestations of a disease or drug

35. Disadvantages of case reports and case studies No control (uncontrolled) Difficult to compare different cases Cases may not be generalizable Selection bias Unknown future outcome/follow-up

36. Clinical trials

37. Clinical trials A clinical trial is any research study that prospectively assigns human participants or groups of humans to one or more health-related interventions to evaluate the effects on health outcomes. Interventions include but are not restricted to drugs, cells and other biological products, surgical procedures, radiological procedures, devices, behavioural treatments, process-of-care changes, preventive care, etc.

38. Why do a clinical trial ? To answer a clinical problem To gain new knowledge about a new or established treatment To support a “claim” For gaining government regulatory approval For marketing a drug, device, or technique

39. Development of a Clinical Trial Idea  Reviews from the experts(Sponsor or CRO)  First planning meeting (basic design features)  Second planning meeting (draft protocol)  Final protocol (ethical and scientific, signed by a statistician)  Evaluation (scientific review, IRB, funding)  Implementation  Final analysis and publication

40. Clinical Trials Design Randomized or Non-randomized Parallel or Cross-over study Blinded (Masking): Single/ Double blinded

41. Clinical Trials: Musk know New Drugs & Clinical Trials 2019 Indian Good Clinical Practice Clinical Trial Registry in India Clinical Trial Compensation

42. Systematic reviews & Meta-analysis

43. Systematic reviews & Meta-analysis Systematic review A systematic review collects all possible studies related to a given topic and design, and reviews and analyzes their results During the systematic review process, the quality of studies is evaluated, and a statistical meta-analysis of the study results is conducted on the basis of their quality Meta-analysis A meta-analysis is a valid, objective, and scientific method of analyzing and combining different results In order to obtain more reliable results, a meta-analysis is mainly conducted on randomized controlled trials (RCTs), which have a high level of evidence

44. Narrative review Systematic review + meta-analysis 1. Questions Broad Focused 2. Search strategy Limited Exhaustive, reproducible 3. Quality assessment 4. Study weight Same weight for all studies Higher weights to precise studies 5. Statistical analysis 6. Bias High Low Narrative vs Systematic review

45. Why do a Meta-analysis or Systematic review? To find out relation between two (or more) variables from pooled available literature To make plethora of information more digestible To settle controversy arising from conflicting studies Increase power & precision Meta-analysis is level-I evidence

46. Flowchart illustrating a systematic review

47. Questions to ask when assessing the quality of a systematic review 1. Was the review conducted according to a pre-specified protocol? 2. Was the question focused and well formulated? 3. Were the right types of studies eligible for the review? 4. Was the method of identifying all relevant information comprehensive?     a. Is it likely that relevant studies were missed?     b. Was publication bias considered? 5. Was the data abstraction from each study appropriate?     a. Were the methods used in each primary study appraised? 6. Was the information synthesized and summarized appropriately?     a. If the results were mathematically combined in meta-analysis, then were the methods described in sufficient detail, and was it reasonable to do so?

48. Pros of Meta-analysis Systematic searches for clinical evidence Explicit and standardized methods for search and selection of evidence sources Thorough appraisal of the internal validity of primary studies Quantitative synthesis with increased statistical power Increased external validity by appraising the effect of an intervention (exposure) across different settings Ability to control for between study variation Including moderators to explain variation

49. Cons of Meta-analysis Adds together apples and oranges GIGO phenomenon: garbage-in, garbage-out Publication bias Not original research Big RCTs definitely better Average effect largely unapplicable to individuals Lau et al, Lancet 1998