Background
- clinical trials – type of epidemiologic study
- planned experiment involving patients and designed to elucidate most appropriate treatment of future patients with a given medical condition.
- Randomized clinical trials
o random allocation of different interventions (treatments or conditions) to subjects
o as long as numbers of subjects are sufficient, this ensures both known and unknown confounding factors are evenly distributed between treatment groups
o can provide evidence of causality
o double blind
Design of a Randomized Trial
- prospective study
o two groups of patients
§ with risk factor
§ without risk factor
o followed into future
o examples
§ prospective cohort study
§ RCT
o outcome has not occurred at the time the study is initiated
Observational and Experimental Studies
- observational – comparing subjects against a control group in cases where researcher has no control over experiment.
- types of observational studies
o case series
o case control
o cross sectional (inc surveys)
o cohort studies
- experiment
o researcher can influence events
o types
§ randomized
§ not randomized
§ self controlled
§ crossover
Design and Conduct of a Randomized Clinical Trial
- randomization
- placebo effects
o must be taken into account in clinical trial design if effects in the intervention group are to be ascribed to the intervention itself, and not to the generic effect of being treated.
Ethical Considerations
- obligations to subjects of research
- obligations to society
- obligations to founders and employers
- obligations to colleagues
Extra Reading – When Are Observational Studies as Credible as Randomized Trials
- observational studies have a record of extremely successful contributions to medicine
- in what circumstances can observational comparisons be as convincing as randomized experiments
- benefits of randomization
o unbiased allocation of treatments à easier concealment of allocation system
§ but does not guarantee that two groups will be equivalent in all relevant prognostic factors
o application of statistical theory on random sampling
- adverse drug reactions – breaking the link between prescription and prognosis
o average randomize trial too small/ does not have sufficient follow up to detect adverse effects that are
§ fewer than one per 200 per year
§ take longer than 1 year to develop.
§ case control studies or large scale observational follow up are required.
o observational study
§ unbiased allocation
· break link between prescription and prognosis
· clinician knows he is prescribing a drug to particular patient
· might not know risk that this particular patient has of developing a particular adverse effect
o intended and unintended effects of treatment
- Proposal for Epidemiology and clinical research – a three pronged restriction
o restriction of research topics
§ observational research should be restricted to questions that can meet the underlying assumption that exposure allocation is unrelated to outcome
· main reason that lung cancern and smoking could be studied observationally might be because people who took up the habit in their youth did so for reasons unrelated to their chances of developing lung cancer.
· was exposure mechanism unbiasesd
§ similar mechanism is known in occupational cohort studies as the heathy worker effect, which leads to lesser disease rates in employed people because of selection and self selection in and out of the workforce.
o restriction in design
§ restrict enrolment to people in whom haphazard allocation of the exposure most likely
Commentary
- complex social and behavioural factors are threats to validity of observational studies
o serving as potential confounding variables associated with both exposure and outcome
Cohort Studies
- cohort à well defined group of people who have a common experience
- prospective
- incidence
- longitudinal
- follow up
- issue of temporality can be resolved
- example
o follow a group of smokers and non smokers over period of time and compare health outcomes
- type of cohort studies
o prospective cohort
§ non current or longitudinal
o restrospective cohort study
§ non-concurrent
§ historical cohort
- key feature
o info about risk behaviours and disease status at baseline known
o compared to outcomes at followup in future
- exposure assessment
o measure of exposure
o outcome
- Advantages
o ethically safe
o subjects can be matched
o can establish timing and directionality of events
o eligibility criteria and outcome assessments can be standardized.
o easier / cheaper than RCT
- Disadvantages
o controls may be difficult to identify
o exposure may be linked to hidden confounder
o blinding is difficult
o randomization is not present
o for rare diseases, large sample sizes or long followup necessary
- Relative Risk
o RR = incidence in exposed / incidence in non exposed
o RR = a/(a+b) // c/(c+d)
o RR ranges from 0 to some positive values
§ 1 à patients in exposed and unexposed groups have same risk
§ greater than 1 à patients in exposed group are at increased risk
§ less than one à patients in exposed group are at lower risk
o RR of 1.4 indicates users were 40% more likely to ….
Comparing Cohort Studies with Randomized Trials
- most experiments, exposure is mostly treatment
- observational à exposure often toxic or carcinogenic agent
- difference à raandomisation
No comments:
Post a Comment