Designing a study I

Research Methods Dent 313

Choosing a research question

First step of research design Identifying a research question

Determine the unknowns in your field What do you wish you knew in your field? What does the available literature lack? Your capacity and experience

Research question

Descriptive Analytic

Descriptive research question

Explaining clinical phenomena

Prevalence of disease

Survival trends

E.g. (Prevalence of caries among school children) E.g. (% of men w prostate cancer alive at 5 years) E.g. (% seniors receiving H1N1 vaccination) E.g. (mean value of LDL among patients w IHD)

Health service utilization

Clinical test characteristics

Analytic research question

Comparative

E.g. (Is prevalence of caries higher among private or governmental school children?) Answering enable to

More significant than descriptive questions

develop intervention to prevent disease Target intervention to particular population

Descriptive questions must be answered first

Choosing a research questions

Specify the population Determine the length of the study and your willingness towards completion

Median time from enrolling subjects to

publication was found to be 5.5 (J.P. Ioanndis)

Choosing a research questions 1st criterion

Choose a question that keeps you excited all the way through

Identify obstacles to performing and

publishing research

Subjects, ethical approval, collaborators, lab

capacity, review committees, editors, missing data

Choosing a research question 2nd criterion

Choose a question that will have an impact on the health and well being of the population
will have before doing it
discoveriesetc

Difficult to fully appreciate the impact a study

Modifications, groundbreaking results,

Purpose of clinical research is to improve

health not for grantsmanship, publication and promotion Enrollment of sufficient number of subjects

Choosing a research questions 3rd criterion

Consider what questions you are ready to answer based on

The prevalence of the disease in your area Your prior experience Your colleagues Your community contacts

Choosing a research questions 4th criterion

Be sure it has not already been answered unless if you can do better

Computerized literature searches Consulting the others in the field Attending conferences
accessible

Scientific / academic relations Not all conference abstracts are electronically

Choosing a study design

There is no best study design Determine the best study design to answer your question
benefits on participants

Feasibility, cost, length of time, risks and Randomized studies Observational studies

Broad categories of study design

Differences between randomized and observational studies

Randomized

Investigator manipulates the condition or

group assignment

One group receives a treatment Another receives a different treatment or placebo

Observational

Investigator assesses a population without

altering the condition or group assignment of the population

Advantages & disadvantages of randomized studies

Better at dealing with confounding and bias Less generalizability Slower to conduct More expensive Cannot answer as broad a range of questions as observational studies

Confounding

Association between a risk factor and an outcome is affected by the relationship of a third variable (confounder) to the risk factor or the outcome Confounder

Associated with the risk factor Causally related to the outcome

Confounding
Risk factor Outcome

Confounder

Randomized group assignment

Outcome

Potential confounder
With randomization there should be no relationship confounder and group assignment

Eliminating confounding

Randomizing subjects Randomization should be unbiased Randomized groups will be equal with respect to confounders Randomization eliminates known and unknown confounders Other techniques for minimizing known confounders

Matching, stratification, multivariable adjustment

Minimizing bias

Randomization eliminates confounding only when unbiased Group assignment should be done

at the time of enrollment not before or after

No group assignment change by personnel

by someone with no contact with the subject using a random number table or generator

Minimizing bias

In observational studies, investigators and subjects usually know which group the subject / examiner were assigned to

Investigators may have some expectation on

what the outcome would be (possibility of bias) Subject may leave the study if they know they belong to control (not treatment) group

Minimizing bias

Blinding in randomized trial

Preventing both the investigator and the

subject from knowing group assignment Double blinded vs. single blinded

Double blinding is impossible with observational studies

Generalizability

Generalizability refers to the ability to apply the outcomes of a study to populations other than the study sample The results of a trial apply only to populations that resemble the study sample

Generalizability and randomized studies

Generalizability is more a problem with randomized studies

Randomized subjects are different from the general population because they carry more burdens

Selection, blinding, previous exams and blood testsetc. Trial subjects receive more attention Treatment works under tight research protocol Treatment efficacy vs. treatment effectiveness

Trial conditions are different from those in clinical practice

Efficacy: how well an intervention works in a research setting Effectiveness: how well an intervention works in a clinical setting

Observational studies and treatment effectiveness

Closer together than in randomized studies Still some differences

Observational study patients receive

additional educational or testing than normal clinical patients Observational study patients may change their behavior (Hawthrone effect)

Length of time to conduct

Observational studies are faster to conduct than randomized studies

Especially

with an existing database and the use of case-control design

Minimizing expenses

Observational studies are less expensive

Especially with an existing database and the use of

case-control design Less markedly with prospectivecohort design

Observers are just observing the outcomes

Randomized control trials are expensive

Paying for all of the interventions

e.g. medicines, tests, appliances..etc.

Addressing a broader range of questions

Observational studies are able to answer a broader range of questions

Many situations where it is unethical or

impractical to randomize subjects (you cannot randomize persons to smoke or not to smoke) Randomized control studies are rarely helpful in identifying causes of disease outbreaks

Indications of observational studies

Instances where it is unethical or impractical to perform a randomized study Time is of the essence in obtaining the results