- Primary research includes:
- Animal or volunteer experiments
- Clinical trials
- Surveys
- Secondary research includes:
- Systematic review and meta-analyses
- Guidelines
- Decision analyses
- Economic analyses
Hierarchy of evidence
- The strength of a study depends on its design
- A hierarchy of evidence exists with decreasing strength as follows:
- Systematic review and meta-analysis
- Randomised controlled trials with definitive results
- Randomised controlled trials with non-definitive results
- Cohort studies
- Case-control studies
- Cross sectional surveys
- Case reports
- Questions regarding:
- Drug treatment or medical interventions require a double-blind randomised controlled trial
- Prognosis require longitudinal cohort studies
- Causation require cohort or case-control studies
Levels of Evidence
| Level |
Description |
| Ia |
Evidence from a meta-analysis of randomised controlled trials |
| Ib |
Evidence from at least one randomised controlled trial |
| IIa |
Evidence from at least one well designed controlled study without randomisation |
| IIb |
Evidence from at least one well designed quasi-experimental study |
| III |
Evidence from well-designed non-experimental descriptive studies such as comparative
studies, correlation studies or case studies |
| IV |
Evidence from expert committee reports or opinions or clinical experiences of respected
authorities |
Purpose of clinical trials
- Clinical trials conduct ‘human experiments’
- Three fundamental principles apply:
- The trial must address a legitimate question
- The patient must be informed and willing to participate
- The patient may decline entry or withdraw at any stage
- There are 4 clinical trial structures
Phase 1 study
- Provides basic pharmacological and toxicology information
- Not a test of therapeutic efficacy
- Performed on either
- Healthy volunteers
- Patients whose disease has progressed on all available treatments
Phase 2 study
- Used to identify dose range of a particular drug
- Sample size is usually about 20 patients
- Patients usually have end-stage disease
- Not usually randomised and drug combinations may be tested
Phase 3 study
- Randomised trial designed to compare effects of different treatments
- One treatment option should be the best currently available
- Outcome measures usually include survival, disease-free survival, response and toxicity
- Usually involve large numbers of patients
- May involve different institutions in several countries
Phase 4 study
- Less commonly used
- Aimed to evaluate the long-term outcome of established therapies
- Often regarded as a post-marketing study
Randomised controlled trials
- In RCT participants are randomly allocated to one intervention or another
- Both groups are followed up for a specified period
- Groups analysed in terms of outcome defined at the outset
- If groups similar at outset any difference should be due to intervention
Advantages of RCTs
- Allows rigorous evaluation of a single variable in a defined patient group
- Potentially eradicates bias by comparing two (or more) identical groups
- Allows for meta-analysis
Disadvantages of RCTs
- Expensive and time consuming
- Often have too few patients or too short a follow-up period
- Surrogate endpoints are often used in preference to clinical outcome measures
- Often imperfect randomisation
- Often not all eligible patients are randomised
- Failure to blind assessors to randomisation status of patients
Cohort studies
- Cohort studies compare groups exposed to different factors
- Followed up to see whether there is a difference in outcome
- Usually used to study disease aetiology
- Also used to assess disease prognosis
Case-control studies
- Case-control studies match patients with a disease to controls
- Data then collected retrospectively to find a difference between the groups
Why are papers rejected for publication?
- The study does not address an important scientific issue
- The study was not original - it had been done before
- The study did not address the authors hypothesis
- A different type of study should have been done
- The sample size was too small
- The study was uncontrolled
- The statistical analysis was inappropriate or incorrect
- The authors drew unjustified conclusions from their data
- The papers was poorly written and incomprehensible
Bibliography
Greenhalgh T. How to read a paper: getting you bearings (deciding what the paper is about). Br Med J
1997; 315: 243-246.
Lilford R, Braumholtz D, Harris J, Gill T. Trials in Surgery. Br J Surg
2004; 91: 6-16. |