All Topics Flashcards
Definition of incidence of a disease
– The rate at which new cases occur in a population at risk during a specific time period – The measure of the populations average risk of disease
Definition of prevalence
The proportion of a population who have a disease at a specific moment of time (Lowered by death and cure)
Define the relationship between incidence and prevalence
Prevalence = incidence x mean duration of disease
How do you compare the incidence in two different groups?
Incidence rate ratio
How do you interpret the incidence rate ratio?
IRR = (8/40000) / (3/30000) = 2Therefore, you are 2 times as likely to die in an exposed region than in the unexposed region
What is a confounding factor?
A factor which is linked to both the outcome and the exposure but is not on the causal pathway
How do you deal with confounding from age and sex?
Use a standardised mortality ratio or standardises morbidity ratio
Define variation
Difference between the observed value and the actual value
What allows for variations?
Error factors
What are confidence intervals?
The values between which we are 95% confident that our actual value lies between
How do you obtain confidence intervals?
- Calculate incidence rate/incidence rate ratio/SMR2. Calculate error factors3. Calculate confidence intervals 4. Interpret confidence intervals
How do you calculate confidence intervals?
Upper bound value = value x error factor Lower bound value = value/error factor
Interpreting a 95% confidence interval when null lies within values
– is null hypothesis within CI (Yes)– are 95% confident that the true value lies within values as it includes the null hypothesis– p>0.05– cannot reject the null hypothesis– results are not statistically significant
Interpreting a value that lies outside the CI
– null hypothesis within CI (no)– 95% certain that true value lies within CI which does not contain hull hypothesis value – p
What does the rate measure?
Absolute risk
What does a ratio measure?
Relative risk
What does a p value
Data is not due to chanceSubstantial evidence against null hypothesisShould reject null hypothesisObservations are statistically significant
What does a p-value > 0.05 signify?
Data is due to chanceNo evidence to reject null hypothesis (can’t accept though) Results are due to chanceObservations are not statistically significant
What is bias?
The deviations of results from the truth via certain processes
What is selection bias?
Error due to systematic differences in the way that the data was collected – allocation bias– healthy worker effect – non-random sample of the population
What is information bias?
Bias due to measurement errors– recall bias – publication bias
What are cohort studies?
Recruit disease-free individuals and classify based on their exposure. Follow up for extended periodsCalculate incidence rates
Advantages of cohort studies
- Compares outcomes based on one exposure2. Can study a range of outcomes for each exposure3. Limits bias4. Measures incidence directly 5. Establishes that exposure precedes the outcome 6. Good for rare exposures
What are the types of cohort studies?
Prospective – recruit disease free individuals then follow upRetrospective – calculate exposure status from historical records then follow up
Disadvantages of cohort studies
- Expensive – large sample sizes2. Not good for rare diseases3. Time consuming4. Prone to losses to follow up
What are the benefits and disadvantages of retrospective studies?
Are quickerMore likely to be affected by confounding
What type of comparisons can you have with cohort studies?
Internal and external
What are the differences between internal and external cohort studies?
Internal has sub-cohorts within the original cohort and you compare an exposed group with an unexposed group e.g. Gulf war syndrome in army vets External compares the cohort with the rest of the population – uses SMR to remove co founders
What is a case control study?
Identify cohort on basis of disease (cases) Identify a cohort of controls who do not have the disease (controls)Compare the exposure status of both the cases and the controls
How do you analyse case control studies and how do you increase the precision of it?
Odds ratio– increase the number of controls up to five per case
Advantages for case control studies
- Good for rare disease but not rare exposures2. Quicker to perform so are cheaper3. Can study multiple exposure for one disease4. Can do nested case control studies (case control within cohort)
How do you calculate the odds ratio?
Exposed cases X unexposed control/ exposed control X unexposed cases A x D/ B x C
What is a nested case control?
A case control study within a cohort study – calculate incidence rate
What is the definition of Bradford Hill’s Criteria?
Minimum conditions needed to establish a causal relationship between two items
What are the nine Bradford Hill’s Criteria?
- Strength of association - stronger association = more likely2. Specificity of association - only with specific factor3. Consistency of association - observed in different studies4. Temporal sequence - exposure proceeds outcome5. Dose response - different levels of exposure lead to different risk of getting outcome 6. Reversibility - removing exposure reduced risk of outcome7. Coherence of theory - association conforms with current knowledge8. Biological plausibility - biologically plausible mechanism is demonstrated 9. Analogy - analogy exist with other disease (similar disease has similar outcome)
Define clinical trial
Planned experience involving patients to find the most appropriate method of treatment for future patients with a given medical condition
What is the difference between controlled trial and cohort study?
Controlled trial – investigator does somethingCohort study – investigator observes only
Purpose of a clinical trial
Provide reliable evidence of treatment efficacy and safety
What are the requirements of a clinical trial?
Must be fair, controlled and reproducible– gives a fair comparison of safety and efficacy
How can two factors be linked?
Due to:1. Unknown confounders2. Common cause3. Reverse causality (think X causes Y but really Y causes X)4. True causal association
What is the definition of epidemiology?
The study of the distribution and determinants of health-related states or events in specified populations and the application of this study to the control of health problems.
What are the items in a hierarchy of evidence?
- Systematic reviews of meta-analysis2. Randomised control trials3. Cohort studies4. Case-control studies5. Cross-sectional surveys6. Case reports
What do you compare your new treatment with in a RCT?
If there is an existing treatment, compare it with that. If there is no treatment, use a placebo.
What are the steps involved in a randomised controlled trial?
- Identify a source of eligible patients2. Invite patients and gain consent3. Allocate to group – new or standard/placebe treatment randomly4. Follow-up each group equally5. Try to keep all the patients in the trial 6. Assess treatments using same criteria7. Compare results:– how big is the difference in outcomes– is difference attributable to treatment?
What can non-random allocation of patients in a RCT lead to?
Confounding factors cause difference in the groups compared
What does random allocation in RCTs give?
Minimal allocation bias – equal likelihood of being in each groupMinimal confounding – groups have same size and characteristics
What can you use to randomly allocate people into groups?
Random number tables, computer generated random number
What types of blinding can you have and when is blinding difficult?
Single, double and triple– in surgery vs. non-surgery or in changes in lifestyle
How can knowledge of the treatment confound results in an RCT?
Patient alters own behaviourClinician alters treatment or care to suit the treatmentInvestigator may alter approach when making comparisons
Describe the placebo effect
The patient may feel an improvement in their health if they feel that someone is doing something to help them even if the therapy is irrelevant to the patients condition
What is a placebo?
An inert substance that has the same characteristics as the treatment
What are the two types of losses?
Unfortunate – patient chooses not to continueAppropriate – clinical condition, requires the removal from trial
How can you avoid losses to follow up?
Clear explanation of requirements, treatment and time commitments. Don’t offer rewards etc. Make follow up as quick and simple as possible Give patient to opportunity to ask questions Maintain contact with patients
What are the ethical implications of using a placebo?
- Should only be used when there is no standard treatment2. Use of placebo is a form of deception3. Patient must be informed that they may receive a placebo
Why may differences in outcomes between treatment groups occur?
- By chance2. Patient may know what treatment they are on - altered behaviour 3. Clinician knows treatment & changes secondary treatment 4. Assessor knows the treatment & investigates differently for each group5. One treatment is better than the other
What twelve characteristics must outcome measures have?
Appropriate and relevant Valid and attributable – effect is linked to treatmentsSensitive and specific – changes are detected accurately Reliable and robust – outcome is messed by diff people in diff places Simple and sustainable – method of measurement is carried out easily Cheap and timely
When does non-compliance occur?
Occurs when patients do not adhere to treatment as prescribed or they may not take it at all.
Hw can non-compliance be reduced?
Clear instructions for treatmentChecks on compliance e.g urine and blood test and table counts Ask about side-effects and effects
What are the two types of randomised trial?
Explanatory and pragmatic
Define an explanatory trial
‘As-treated’ analysis– is the physiological action of the drug better than the new drug?– non-compilers are excluded– trial is affected by confounding as groups are no longer allocated randomly
Define a pragmatic trial
‘Intention-to-treat’ analysis– would replacing the standard drug with the new drug benefit patients in clinical practice?– see real world effect of the treatment – should analyse the whole group regardless of whether they took the drugs or not– randomisation is preserved
What analysis should be used for RCTs?
Intention-to-treat analysis – randomisation is preserved– confounding does not affect results – represents standard clinical practice
What are the three ways that you can define outcomes?
- PATHO-PHYSIOLOGICAL e.g. Tumour size, thyroxin levels2. CLINICALLY DEFINED e.g. Mortality, morality, disability3. PATIENT FOCUSSED e.g. Quality of life (included in all cancer trials), psychological and social well-being, satisfaction
When do you measure outcomes in a RCT?
Beginning – baseline measurement Throughout trial – possible and adverse effects (is one group disadvantaged, are individuals being harmed?)End of trial – final measurement of outcomes
Why does non-compliance occur?
Misunderstood instructionsDon’t like taking treatmentThink treatment isn’t workingPrefer another treatment Can’t be bothered to take treatment
Describe the differences between as-treated vs. intention-to-treat analysis
As-treated give larger sizes of effect Intention-to-treat gives smaller, more realistic sizes of effect
What are the four ethical principles that govern individual care?
Principal of beneficence – do goodPrincipal of non-maleficence – do no harmPrincipal of autonomy – let the patient decidePrincipal of justice – be fair
What issues should be considered to have an ethical clinical trial?
Clinical equipoiseScientifically robustEthical recruitmentValid consentVoluntariness
What is clinical equipoise?
Reasonable uncertainty into which drug is better for the patient– not subjecting patients to a treatment that is less effective or harmful– includes non-intervention
Describe ‘scientifically robust’
The pursuit of knowledge for the good of the general population – address relevant and important issue– ask a valid question– appropriate design and protocol – have potential to reach sound conclusions– justify use of comparative treatment– have acceptable risks of harm compared to future benefits – have provisions to monitor patient safety & well-being– have arrangements for appropriate reporting and publication
What are the two main issues involved in ethical recruitment
Inappropriate inclusion and inappropriate exclusion
Give example of inappropriate inclusion in RCTs
- Participants who are unlikely to benefit e.g. AIDS treatment in Africa 2. Participant with a high risk of harm compared to potential benefits e.g. Pregnant women3. Participants likely to be excluded from analysis e.g. Small sub-groups of the population
Give examples of inappropriate exclusions in RCTs
- People who differ from ideal homogenous group e.g. Non-white people, women, elderly (co-morbidities so hard to isolate disease)2. People who are difficult to obtain valid consent from e.g. Immigrants (language issues), children, mentally ill, prisoners
Describe valid consent
Patients must have sufficient knowledge given by a knowledgeable informant and have been given a cooling-off period. Must be able to ask questions and know they can opt out at any point. Must get written and verbal consent.
What do you need in order to gain consent?
Informed participantCompetent decision makerLegitimate authoriser – usually the same person unless child, elderly, mentally ill when you can have different people in each role
What is signed consent evidence of?
Evidence of valid consent but it is not valid consent in its own right. Consent must be both written and verbal.
Define voluntariness
For consent to be valid, the decision should be free from coercion and manipulation as well as the perception that coercion and manipulation took place.
What are examples of coercion?
Non-access to best treatmentLower quality of careDisinterest of clinician
Examples of manipulation
Exploitation of emotional stateDistortion of informationFinancial inducements
What is the main responsibility of a research ethics committee?
The ensure that research respects the dignity, well-being safety and rights of participants
What factors do research ethics committees focus on?
- Scientific design and conduct of study2. Recruitment of participants3. Care and protection of participants4. Protection of the confidentiality of participants5. Informed consent process6. Community consideration (must be able to use treatment in the future)
Why do we have a moral obligation to participate in clinical trials?
We have benefitted from previous studies so we have an obligation to take part to benefit the patients of the future
What is a systematic review?
Secondary research that is an overview of primary studies that used explicit and reproducible methods – large no. of studies identified then narrowed down to most relevant and credible
Define meta-analysis
A quantitative synthesis of results of two or more primary studies that addressed the hypothesis in the same way– provides an overall, combined value for all the primary studies with confidence intervals
What type of studies do systematic reviews usually combine?
Cohort studies, randomised control trial and case-control studies
Give the advantages of systematic reviews
– explicit methods reduce bias and exclusion of poor quality studies– large amount of info is assimilated quickly – reduction in time between research discovery end implementation in clinical practice – used in evidence based practice guidelines
What are the key aspects of a systematic review?
It is:TransparentReproducible Explicit
Describe the characteristics of a systematic review
Has a clearly focussed questionExplicit statements about: type of study, participants, interventions and outcome measuresSystematic search for literatureAppraisal of trialsSynthesis of conclusion and outcomes, sometimes with meta-analysis
What is the purpose of a meta-analysis?
– allows synthesis of large number of study results– systematically collate study results– reduce problems of interpretation due to variation in sampling – quantify effect sizes and uncertainty as pooled estimate
What does weighting do in meta-analysis?
Allows to to compare sizes of studies, how uncertain reviewers are about odds ratio and how important they are E.g. Smaller error factor = greater weight to result
Why are systematic reviews important?
Are crucial in evidence based medicine
How is the data from a meta-analysis collated?
In a forest plot
How do you interpret a forest plot?
– odds ratios and CIs are given for each study (square with line)– size of square equates to weight given to study– diamond is pooled estimate (centre is OR, width is CI) – solid line is null hypothesis
What causes heterogeneity between studies?
Studies are not identical and are usually have variation within the data
What are the two models you can use in meta-analysis?
Fixed effects modelRandom effects model
What is the fixed effects model?
Assumes studies are homogenous and variation is due to within study variation– assumes studies are estimating exactly the same effect size
What is the random effects model?
Assume studies are heterogenous and and variation is due to within-study and between-study variation. – assumes studies are investigating similar effect size
How can the quality of studies used for systematic review be affected?
Poor study designPoor design protocolPoor protocol implementation
How can you determine publication bias?
Using a funnel plot for studies used in a systematic review Well-balanced review (published and unpublished) will show a balanced funnel shape A biased review will vary in shape
How do you ensure that your systematic review is of a high quality?
Include studies above a quality standardAssess impact of quality on pooled effect
Disadvantages for case control studies?
Does not establish that ensure precedes outcome Bad for rare exposures Prone to selection and information bias Relative risk only
