quality education for a healthier scotland pharmacy critical appraisal level 2 evaluating studies...

Quality Education for a Healthier Scotland

Pharmacy

Critical Appraisal Level 2

Evaluating studies using the Critical Appraisal Skills

Programme (CASP) Tools


Pharmacy

What is Critical Appraisal?

Critical appraisal is the process of systematically examining research papers before using the evidence to form a decision

Critical appraisal allows us to make sense of research evidence and close the gap between research and practice


Pharmacy

Why Critically Appraise?

• In evidence based medicine the clinician should use the best available evidence to decide which treatment option is best for their patient• To determine the best treatment option we must have critical appraisal skills to assess the quality of research


Pharmacy

Advantages of Critical Appraisal

• Provides a systematic way of assessing the validity, results and usefulness of published research • Allows us to improve healthcare quality• Encourages objective assessment of the usefulness of all information/evidence• Critical appraisal skills are not difficult to develop – mostly common sense!


Pharmacy

Disadvantages of Critical Appraisal

• Can be time consuming• It may highlight that current practice is in fact ineffective• May highlight a lack of good evidence in an area of interest


Pharmacy

Help with Critical Appraisal

• It is difficult to remember all the issues which must be taken into account when reading research papers • To help with this the Public Health Resource Unit

in Oxford have produced tools to evaluate most types of study as part of the Critical Appraisal Study Programme (CASP)• These are called CASP tools


Pharmacy

CASP Tools

• CASP Tools have been developed to help us appraise:• Systematic Reviews• RCTs• Case-control studies• Cohort Studies• Tools for other types of study (e.g. qualitative research, economic evaluations and diagnostic studies) are also available


Pharmacy

CASP Tools (2)

The tools break critical appraisal of each study type into 10-12 manageable questionsThe questions in each tool will vary slighty as study designs are differentThey are available at:http://www.sph.nhs.uk/what-we-do/public-health-workforce/resources/critical-appraisals-skills-programme


Pharmacy

Randomised Controlled Trials (RCTSs)

RCTs are the best type of research study to determine if a specific intervention produced the desired outcome in a specific population

e.g. The HOPE study: Does ramipril (the intervention) prevent myocardial infarction, stroke or death from cardiovascular causes (the outcomes) in patients who were at high risk for cardiovascular events but who did not have left ventricular dysfunction or heart disease (the population)


Pharmacy

RCTs (continued)

RCTs should have a clearly defined research question in relation to the population, outcome and intervention

RCTs can minimise bias and use the most appropriate study design for investigating the effectiveness of a specific intervention or treatment

RCTs are, however, not automatically of good quality and should be appraised critically


Pharmacy

Appraising RCTs

Three broad issues should be considered when examining a report of an RCT:• Validity• Results• Relevance• The CASP tool prompts us to ask questions

which will assess each of these issues in more detail


Pharmacy

Screening Questions in CASP tool

Questions 1 and 2 in the RCT CASP tool are screening questions to assess if:The RCT asks a clearly focused study question (i.e. is population, intervention and outcome being investigated clearly stated?)Whether an RCT is the most appropriate study design to ask this questionIf the answer to either of these is “no” then it is probably not worth continuing with the rest of the questions


Pharmacy

Validity

When assessing validity the methods used in the study are appraisedIf the research methods are flawed then this may invalidate the results of the trialTo critically appraise the methodology of an RCT you will look at sample size, randomisation and baseline characteristics, blinding, follow-up, data collection and interventions. These elements are dealt with by questions 3-7 in the CASP tool for RCTs


Pharmacy

Randomisation and Baseline Characteristics (Q3 in CASP Tool)

Randomisation reduces the possibility of biasMethod of randomisation should be robust and neither the participants or clinicians should be aware which group patients will be in before randomisationMost robust methods are computer- generated numbers or tables of random numbers (gives 50:50 chance of being in either group)Stratification can be used to ensure similar baseline characteristics in both groups


Pharmacy

Randomisation and Baseline Characteristics (Q3 in CASP Tool)

The make-up of treatment and control groups should be very similar and the only difference should be the intervention under investigation in the studyThis is so that we can be confident that the outcome is due to the intervention and not to any other confounding factorsConsider:Is the sample large enough? (see also Q7)Was the randomisation process robust? Was there stratification?


Pharmacy

Blinding (Q4 in CASP Tool)

If the people involved in the study are not aware who is in the treatment or control group this reduces the possibility of bias i.e. ideally a study should be double-blindSingle-blind and open-label studies would be expected to have higher chance of producing biased resultsTo blind patients and clinicians the intervention and placebo must appear to be identical – this is not always possibleConsider – if every effort was made to achieve blinding-if it matters in the study being reviewed (i.e. could there be observer bias in the results that are used?)


Pharmacy

Follow-up (Q5 in CASP tool)

If a large number of participants withdraw from a trial before its conclusion their loss may distort the results

Crossover between groups can also distort the results as the effects of randomisation can be lost

In most cases intention-to-treat analysis should be used – i.e. the final results should be analysed according to the original randomisation


Pharmacy

Interventions (Q6 in CASP tool)

It is important that, aside from the intervention under investigation, the groups are treated equally as this means the outcome of the study can be attributed to the intervention

Consider:• Were groups reviewed at the same time intervals?• Were any other treatments allowed in either group?


Pharmacy

Interventions (Q6 in CASP tool)

Also consider:• If tests or measurement s were used were they conducted by appropriate personnel and established tests were used?• Were assessments frequent enough to show a pattern of response?• Is the duration of the study sufficient?


Pharmacy

Sample Size (Q7 in CASP tool)

• A study should include enough participants so that the researchers can be reasonably sure that there is a high chance of detecting a beneficial effect

• A power calculation should be carried out before the participants are enrolled to estimate how many people need to be recruited to achieve a certain level of

certainty (usually aim for 80-90%)


Pharmacy

Results

The results of a RCT should be scrutinised in a similar way to the method

Broad considerations are:• What are the results?• How are the results presented?• How precise are the results?

This is dealt with by questions 8 and 9 in the CASP RCT tool


Pharmacy

Presentation of Results (Q8 in CASP tool)

Results can be expressed as:• Relative Risk – if we hope that the intervention will lead to LESS outcomes (e.g. MI, stroke, death) we want a hazard ratio of less than 1• Absolute Risk – proportion of people experiencing an event in each groupResults may be reported as either of the above or as both


Pharmacy

Presentation of Results (2)

The results presented should relate to the objectives set out in the original description of the study methodRelative or absolute measures may have little meaning in relation to clinical practiceNumbers needed to treat (NNT) may make measures more understandableNNT is the number of people who must be treated to produce one additional successful outcome


Pharmacy

Precision of Results (Q9 in CASP tool)

Statistical tests are used to establish whether the results of a trial are real or whether they occurred purely by chance

There will always be some doubt as the trial only looks at a sample of the population

Confidence intervals and p-values indicate the level of certainty around the results


Pharmacy

Confidence Intervals (CI)

Inferences based on random samples are uncertain because different results would be obtained each time a study was repeatedCIs indicate the range of doubt around the results and represent the range of values within which the true value liesTherefore, the narrower the range, the more convincing the resultsIf CIs overlap this indicates that the study has failed to demonstrate a difference


Pharmacy

P-values

P-values describe the probability that a result has happened by chance

P<0.05 is usually described as statistically significant and means that the results are unlikely to be due to chance


Pharmacy

Statistics Used

There should be adequate statistical analysis of the relevant results and the statistical analysis used should be appropriate to trial size and design

Statistical tests used should be adequately described and referenced

Consider whether a statistician is listed as one of the authors


Pharmacy

Clinical vs. Statistical Significance

A statistically significant difference in favour of a drug does not always indicate a clinically significant differencee.g. in a study of two antihypertensives a difference in BP of 1-2mmHg may be statistically significant but is this likely to confer significant clinical benefit?Also consider surrogate markers versus clinical endpoints (e.g. an increase in bone mineral density versus a decrease in fracture rate)


Pharmacy

Relevance

If the methodology and results are acceptable then the applicability of the results to the local population should be consideredSome broad issues include:• Relevance to the local population• Were the outcomes considered clinically important?• Risk versus benefit of treatmentQ10 in the CASP tool prompts us to consider the issues around the relevance of our study to our local population


Pharmacy

Relevance to Local Population

It is important to consider if there are any differences between the participants in the trial and the local population that would make it impossible to apply the results locally. Think about:Inclusion/exclusion criteria – e.g. age, ethnicity, co-morbidities, concomitant medicationLocal healthcare provision – the setting may have been in a different healthcare system and it may not be possible to provide similar care locallyControl group – is the standard treatment used in the study better or worse than local standard? Are realistic comparative doses used?


Pharmacy

Importance of outcomes

Were all clinically important outcomes considered? A single RCT is unlikely to address all the clinically important outcomes but consider if the original question has been answered and if any other important outcomes have been missed out.

Think about outcomes form the point of view of:• The patient and their family/carers• The clinician using the treatment• Policymakers• The wider community


Pharmacy

Risks versus BenefitsRisks:Safety – the risk of serious side effects may outweigh the benefits of treatment (can calculate NNT vs. NNH)Tolerability – what was the drop-out rate in the study compared to withdrawal rates on the current standard treatment?Is the benefit of the treatment large enough to outweigh these risks?


Pharmacy

Other Considerations

Cost implications – financial information is not normally included in a trial. Economic evaluations may be availableSimplicity of use – patient factors such as compliance, method of administration or complicated devices may limit the usefulness of a treatment in clinical practiceQuality of life data – gives more information from the patient’s perspective Sponsorship – sponsorship of the research or author affiliations to drug to drug companies may affect how the results are presented


Pharmacy

Look out for……..A lot of work and funding goes into drug development and clinical trials and drug companies and researchers will want a positive result from their hard workWhen apprasing RCTs beware of the negative aspects of the study being glossed over to make it appear positive. This can include:1. Use of sub-group analysis2. Use of composite end points3. Analysis of secondary outcomes


Pharmacy

Sub-group analysis

Sub-group analysis is when results are broken down into patient sub-groups e.g. elderly, patients with a history of stroke/diabetesIf the result of the overall trial is negative it may be positive in a specific sub-groupTrials may not be powered to detect differences in sub-groups containing small numbers of patients


Pharmacy

Use of Composite Endpoints

Sometimes the desired outcome of a clinical trial is relatively rare e.g. fatal MITo show a difference between intervention and control huge numbers of participants in very long term trials would be requiredComposite end-points may be used instead e.g. risk of MI, stroke, death or hospital admission due to cardiac causesNot all the individual components are always of equal importance to all patients


Pharmacy

Analysis of Secondary Outcomes

The primary outcome is the most important outcome of an RCTIf no statistically significant increase in efficacy is observed with the new treatment then secondary outcomes which are significant may be quoted in the resultsThe number of patient enrolled in a trial is based on the primary outcomeIt is poor practice to disregard the primary outcome and quote a secondary outcome as the main result


Pharmacy

Remember!

Healthcare decisions are not usually made on the basis of one trial. Other factors and other evidence may also have to be considered when making a decision


Pharmacy

Appraising other publications

In addition to RCTs other publications may be used to contribute to evidence-based decision makingIn order of importance the usual hierarchy is: Systematic reviews RCTs Observational studies e.g. cohort, case-control or cross-sectional studies Case reports, case studies Expert consensus


Pharmacy

Systematic Reviews

Systematic reviews seek to bring the same level of rigour to reviewing research evidence as should be used in producing research evidence. They:

• Identify relevant published and non-published evidence

• Select studies for inclusion and assess the quality of each

• Present a summary of the findings with due consideration


Pharmacy

Systematic Reviews (2)

Meta-analysis is a statistical technique for combining the results of independent studies and is the technique normally used to combine the results of selected studies for systematic review.Validity of meta-analysis depends on the quality of the systematic review on which it is based.Like RCTs systematic reviews should not be considered to automatically be of good quality and should be critically appraised.


Pharmacy

Observational Studies

Includes cohort studies, case-control studies and cross-sectional studies

These studies lack the controlled design of RCTs and the evidence which comes from this type of study is therefore considered less robust

In some cases observational studies provide the only evidence available (e.g. emerging safety issues) and therefore it is also important that we are able to critically appraise these


Pharmacy

Over to you……

Now use what you have learned from this presentation and the tools available online to critically appraise a randomised controlled trial and a cohort study

quality education for a healthier scotland pharmacy critical appraisal level 2 evaluating studies...

Documents