Evidence Based Practice

Introduction for residents

Judith Riley, OD

[email protected]

918 527 7210

• The roots of EBP are in Epidemiology. The set up and use of studies to evaluate populations, treatments, testing, and therapies, looking for outcomes, diagnosis and prognosis.

• What studies can do this? Experimental and observational. The study used depends upon the information being sought.

Experimental vs. Observational Studies

Were exposures assigned by investigators? Once this happens the study becomes experimental.

If a natural course of the disease is being followed without interference by the investigator, the study is observational.

Experimental vs. Observational studies

Experimental are useful for clinical knowledge as far as what choice in treatment, what dose, how long to treat.

Observational studies lead to knowledge as to the etiology and risk factors for human disease. Who gets disease? What are the risks for morbidity and mortality?

Types of Experimental Studies

1. Non Randomized trial: subjects are knowingly assigned to the control or trial group. This can lead to bias in the findings.

2. Randomized trial: The subjects are assigned to groups in a masked/blinded fashion: be it single, double blind or triple blind. This leads to less bias in the findings. Not appropriate with toxic or carcinogenic agents, it would be unethical to assign a known carcinogen.

Randomized Clinical Trial

Current Treatment Study Population Randomly Assigned New Treatment Do not Improve Improve Do not improve Improve

Use of Randomized trials

• New drugs • Non medication treatments of disease • New technology • Screening programs • New ways of organizing care • New delivery services • Randomized clinical trials are for more than just patient care as compared to Randomized trials.

Selection of subjects in a random study

Should be well documented in writing and direction so others may follow in the future.

No element of subjective decision making on the part of the investigator as to whom is included or not. We want to trust the results and be able to repeat them.

Masking or Blinding

• Once subjects are assigned they should not know which group they are being assigned to.

• Placebos may be used to help mask.

• The observers or data collectors should not know which group a patient is in or the subject. “Double blinding”.

• In a triple blinding; subject, data collectors and data analyzers do not know who is in which group.

Crossover

•

Planned crossover

: after being on treatment for a while, the patient is crossed over to the other therapy and observed with it. Each patient acts as their own control.

• • Carryover from previous therapy must be accounted for. (prostaglandin in gl) Also patient enthusiasm may be better for first treatment.

Unplanned crossover

treatment during study by subject choice or clinician.

: subjects change

Generalizing the results of the study to the general population

• •

Internal validity

: study was properly done without major methodologic problems. The study size was good, comparison groups were valid. Findings are valid.

External validity

: the new therapy is better for the disease treatment regardless of where the patients are treated, not just for the study group. It can be generalized to the entire population.

FDA phases •

Phase I

; clinical pharmacologic studies of small groups (20-80) looking for toxic and pharmacologic effects. •

Phase II

; clinical investigations of 100 to 200 patients for efficacy and relative safety.

•

Phase III

; large-scale randomized controlled studies for effectiveness and relative safety which are often multicentered

• Licensed after passing Phase III • Unfortunately some adverse effects such as carcinogenesis and teratogenesis may not manifest for many years.

• Phase IV studies are post marketing surveillance to monitor new agents as they are used for treatment.

• Avandia , almost recall this summer.

Publication bias

• Not all results of clinical studies are published • Erroneous conclusions may be drawn if only one side is published.

• Dramatic results are more likely to be published.

• Funding may affect what is published.

• All clinical trials of medical interventions must be registered in a public trial registry before any participants are enrolled.

Review: Contact Lens Spectrum

• What makes a trial valid?

• Design and Randomization • Control of Variables • Masking • Number and composition of subjects • Good analysis and true representation of results • Meaningful results • Validity to your patient

Types of observational study designs

• Cohort study: analytical study • Case-control study: analytical study • Cross-sectional study: analytical study • Case study: descriptive study

Types of Observational Studies

Are groups set up and chosen to be observed? Yes…..this becomes an analytical study as now comparisons are being made between the two groups.

No……this becomes a descriptive study and usually is used to develop hypothesis for future studies.

Analytical Observational Studies

The direction of the study determines the type of study: 1. If you first look for exposure, and then check the outcome:

Cohort Study

. This is good to find causal relationships.

2. If you first look at the outcome and then go back and check for exposure, this is a

Case Control

study and is good for studying rare diseases.

3. If you look at the exposure and the outcome at the same time, this is a

Cross-Sectional

study and you can identify prevalence with it.

Cohort study

• A group of exposed individuals and a group of nonexposed individuals are identified and followed up on to compare the incidence or rate of death from disease in the two groups. • If a positive association exists between the exposure and the disease, the proportion of the exposed in whom the disease develops should be greater than in the nonexposed group. Great for finding the cause of a disease.

Cohort compared to Randomized Studies

• Both studies compared exposed and non exposed groups.

• Studies with harmful exposures can not be randomized such as carcinogens so cohorts can be used ethically. Lifestyle choices lead to some people having desired exposure for study.

• When not performing a randomized study questions are often left unanswered. Are other factors besides the tested exposure leading to conclusions?

Disease

Cohort Studies

Defined Population Nonrandomized Exposed Not Exposed No disease Disease No disease

Prospective Cohort Study

• Also called

concurrent cohort or longitudinal study.

• A defined population is chosen and then followed over time. First seeing who develops the disease and then what course the disease takes. • This type of study takes many years.

• Exposure and nonexposure are found as they occur during the study.

Retrospective Cohort Study

• Also called

historical cohort study or nonconcurrent prospective

study.

• Use past data and histories to establish data.

• Exposed and nonexposed cases are still compared, less time is needed. • Exposure is ascertained from past records and outcome is known when the study begins from existing records.

Biases in cohort studies

1. Bias in assessment of the outcome: observer knows exposure in subjects, biasing outcome.

2. Information Bias: quality of information should be equal between exposed and nonexposed. Subjects may be the source of information bias. Poor information given.

3. Biases from nonresponse and losses to follow up: poor subject response to survey and lost subjects 4. Analytic Bias: strong preconceptions may lead to bias in interpretation of results.

Case-Control Studies

• • Case studies or case series are a way to observe the course of the disease.

• With out a comparison or control group conclusions are not reliable.

Comparison

is an essential component of epidemiologic investigation, case-control study design uses comparison. Case studies do not.

Design of Case-Control Study

Cases Have the disease Controls Do not have the Disease Were exposed Were not exposed Were exposed Were not exposed

Sometimes a Case-Control study is called a backward Cohort as in cohort the exposure is first identified and then the disease. Case-Control first identifies the presence of disease and then the exposure.

What case-control is not

• This is not a measurement of prevalence.

• The number of controls is chosen by the investigator and does not reflect the prevalence of the disease in the population.

• It is not a cohort test as the study begins with people with the disease and compares them to people without the disease. Cohort studies work with exposed and non exposed people and follows them for development of disease over time.

• Case-control studies are valuable when disease is rare.

• Cases may be easy to locate from established records.

• Case-control studies are usually faster than cohort studies.

When to use case-control studies

• First step when searching for cause of an adverse health outcome.

• Compare people with disease and people without the disease.

• Figure out which exposure or characteristic is causing the disease.

• Once the relationship is documented, then a more expensive cohort study may be done to explore if exposure is linked to the disease.

Cross-sectional studies

• The characteristics of a population are studied at one time point, this study can be used to document prevalence.

• Exposures, disease and outcomes can all be studied.

• Useful for determining health care needs.

We have studies,

Using the strengths of the different forms of studies, questions about patients can be answered. We can look for population characteristics, treatment options, comparisons and expected outcomes Evidence based practice turns information from studies into clinical decisions and application.

Archie Cochrane • MD/ Epidemiologist from Scotland • In 1972 published: ”Effectiveness and Efficiency” bringing attention to the bad effects in health care from lack of available evidence.

• “It is surely a great criticism of our profession that we have not organized a critical summary, by specialty or subspecialty, adapted periodically, of all relevant randomized controlled trials”

• An international systematic review of clinical trials by specialty was his proposal for improving health care.

• In the 1980s, Iain Chalmers set about starting the pilot of Effective Care in Pregnancy and Childbirth, the first area of clinical practice reviewing RCT’s.

• This review exposed gaps in care between research and clinical practice. This led to belief in the benefits of evidence based practice.

Corticosteroids for preterm birth

1972 1972 to 89 1989 A published RCT showed improved outcomes for premies when steroids used prior to birth 6 more RCTs confirmed this. Most OB’s did not know this.

The first systematic review of corticosteroid treatment published Seven more studies published.

1989 to 91

Corticosteroid treatment reduced the odds of babies dying from complications of immaturity by 30 to 50%. But due to lack of the information getting to the doctors, thousands died because the 1972 study was not well known. Meta-analysis of these studies helped the use of steroids become a standard.

Clinical Decision Making

• What test is the best to explore the condition the patient presents with?

• Which treatment would be the most effective?

• The practitioner’s knowledge base, skills, attitudes, resources, patient’s expectations and concerns all feed into the decision.

Doctor’s knowledge of evidence, skills, attitude Health system access rules Clinical decisions Patient values, concerns, expectations Concern about litigation

A definition from David Sackett, McMaster University, Ontario , Canada: Evidence Based Medicine

: integrating individual clinical expertise with the best available external clinical evidence from systematic research to achieve the best possible patient management. Dave Sackett

1990: Sackett’s “Just in Time” learning An EBM Approach to Education

• Evidence cart on ward rounds - 1995 • Looked up 2-3 questions per patient • Took 15-90 seconds to find • Changed about 1/3 decisions • Rounds took longer!

Evidence Based Medicine or Evidence Based Practice

Using the term Evidence Based Practice is more inclusive of different areas of health care practice. The term practice encompasses more than just physiological, anatomical or biochemical processes found in medicine. Practices covers outcomes of clinical activities that are greater than just medicine.

Using Evidence Based Practice

1. Acknowledge that there are uncertainties in clinical knowledge. Both in self knowledge and in changes to knowledge from new findings.

2. Use research information to reduce uncertainties.

3. Know which information found is strong and which is weak.

4. Determine probabilities of uncertainties.

New clinical skills in using EBP

1. Efficient literature searching.

2. Application of formal rules of evidence in evaluating the clinical literature.

What skills are currently being used?

• Attending journals and conferences • Reading journals • Information from pharmaceutical representatives • Textbooks • Published clinical guidelines • Electronic searching • Small group learning • Talking to other colleagues

Finding the best information for the clinical questions you have.

Questions arise as patients are evaluated and treated. How many question on average arise?

In a study of 103 Iowa GPs, in 2.5 days 1101 questions were generated. 702 questions were pursued for answers in print and from human resources. Less than 2 minutes were spent on finding these answers. Of all these questions, only 2 led to a formal literature search.

Information seeking habits Physicians report 2 questions for every 3 patients.

Observation shows usually 5 questions for each patient.

Only 30% of questions were answered, usually by asking a colleague Textbooks were thought to be too old, lack of time to find answers, and lack of knowledge of where to look were given as reasons for not finding answers.

Back to the cart

David Sackett in 1998, with his evidence cart reported that with 71 information searches to answer clinical questions, 52% confirmed the management decision, 25% led to a new therapy or treatment plan, 23% corrected a previous plan.

S. Crowley in 2003, with CAR study showed that 520 clinical questions when the answers were sought in medical literature 53% confirmed the patient management, 47% the medication, diagnostic, or prognostic information was changed.

The Study Data of 145 cases and clinical decisions

• 31 could be supported by a randomized controlled trial • 65 were supported by a head to head trial (not a placebo-controlled trial) • 23 were supported by case-control or cohort studies • 4 were supported by case series reports • 22 could not be supported by a literature study

Use of Randomized clinical Trials to determine probable clinical outcomes in treating patients.

20,000 trials are published each year.

In 2005, 55 new trials published every day.

Reading every trial would be impossible, so methods to find the most important trials for the the questions that arise in practice are needed.

Developing clinical questions and then searching current databases may be more productive way of keeping current

.

• EBP will change how literature is used. The use of literature to answer individual patient questions will expand the clinician’s individual knowledge base.

Optometric Application

• “Whither Goes Evidence-Based Optometry” • In the April 2009 issue of Optometry and Vision Science, Editor Anthony Adams makes his case for the use of Evidence Based Optometry to find the best research and utilize the research to diagnose and provide therapy.

• Refer to attached article.

What happens when there is no evidence?

Behavior Optometry: from Wikipedia Is an expanded area of optometric practice that claims to use a “holistic” approach to the treatment of vision and vision information processing problems. The practice of behavior optometry incorporates various vision therapy methods and has been characterized a a complementary alternative medicine practice. A review in 2000 concluded that there were insufficient controlled

studies of the approach and a 2008 review concluded that “ a large majority of behavioural management approaches are not evidence based, and thus cannot be advocated.” 2008 review: Brendan Barrett, “ a critical evaluation of the evidence supporting the practice of behavioural vision therapy” Ophthalmic and Physiologic Optics 29

Listing of upcoming education at the Colorado State Seminar, 2010

• Live by the Evidence; Research and Practice • COPE #27540-GO • As doctors we are told we should use evidence based medicine in clinical care. However, it is difficult in this fast-paced world to get quality information to apply to decisions about patient care. This course will model a streamlined approach to defining “good science” with cases and examples of evidence-based medicine in eyecare.

AOA

• Plans are in place to change Clinical Guidelines to an Evidence Based Web site much like the ADA page. This will have all clinical guidelines in EB form, hopefully in 2 years.

• New questions will be constantly researched • Eventually the practitioner may post their own questions for research.

It all begins with a question.

–

Formulate Clinical Questions

– Search for Evidence – Appraisal of research – Apply to clinical problem

Step 1 Formulate an answerable clinical question

• Structure of researchable questions –

PICO

–

P

opulation/Patients –

I

ntervention –

C

omparison –

O

utcome

Patients/Population

• Identify the patient /population characteristics that will affect your question.

Intervention

• Is there a treatment/therapy you are considering or want to know more about?

Comparison

• Do you want a comparison between two therapies?

Outcome

• Are you or the patient wanting to know the outcome of the disease or the treatment options?

Question Structure: PICO

P

atient

O

utcomes

I

ntervention

C

omparison

Type of questions will lead to the type of study that will answer the question.

How to select and interpret diagnostic tests Diagnosis Therapy Prognosis Harm/Etiology How to select treatments to offer patients that do more good than harm and that are worth the efforts and costs of using them.

How to estimate the patient’s clinical course and complications How to identify causes for disease

Evidence pyramid

Meta-Analysis Systematic Review Randomized Controlled Trial Cohort Studies Case Control Studies Case Series/ Case Reports Animal Research/ Laboratory Studies

Evidence Pyramid

Information usually starts with an idea or laboratory research. The ideas turn into drugs or tools that are tested in labs, in animals, and finally in humans. The human testing may go to clinical trials.

As you move up the pyramid the amount of available literature decreases, but increases in its relevance to the clinical setting.

New Terms

• Meta-analysis: examines a number of valid studies on a topic and combines the results using accepted statistical methodology as if they were from one large study. This not only uses information from RCTs, but also appraises their validity.

• Systematic Reviews: focus on clinical topic and answer a specific question. An extensive literature search is conducted to identify all studies with sound methodology. The studies are reviewed, assessed and results summarized. The Cochrane Collaboration has done many studies for systematic review topics and includes 144 on vision and eye.

Type of question leads to study design

Type of question Best type of study Therapy Diagnosis Risk factors RCT>cohort>case control>case series Prospective cohort, blind comparison to a gold standard cohort>case control>case series

Prognosis Prevention Clinical Exam Cost cohort>case control>case series RCT>cohort>case control>case series Prospective cohort, blind comparison to a gold standard Economic analysis

What are your clinical questions?

Your 59 year old black patient is concerned that he might have glaucoma. His older sister had glaucoma and went blind.

Could he have glaucoma and will he go blind like her sister?

Types of questions: glaucoma

What are the risk factors for glaucoma?

•

Cohort Study

• Will I go blind?

Prognosis

•

Prospective Cohort Study

How should this patient be treated? Eye drops, laser, surgery? Treatments, Therapy

Randomised Trial

When meta-analysis or systemic review is done, the value of the information increases.

2. Searching: finding good answers?

Should I ask a colleague?

• 12 occupational therapy questions – E.g., Is a 38-year old sewage worker subject to a higher risk of contracting Hepatitis A as a result of occupational exposure? (No) • Obtain advice from 2 professionals on 3 cases each.

• 37% wrong answers – 17% wrong if based on literature – 65% wrong if not

Searching made easy



3. Rapid Critical Appraisal

It’s peer-reviewed, therefore it must be OK?

Step 3: Appraise the evidence

• Did you find good quality studies?

.

Two steps.

Did you ask good questions?

PICO Was the research valid?

What makes a good study?

• Lack of Bias and confounding • Internal validity in the design, randomization, blinding, accuracy in testing and reporting.

• External validity in translating to the real world.

Is there internal validity?

• Was the assignment of patients to treatment randomized.

• Were all the patients who entered the trial properly accounted for at its conclusion? Good follow-up?

• Were patients analyzed in groups to which they were assigned?

• Were patients, clinicians and study personnel blinded?

• Were the groups similar at the start of the trial?

• Were the groups treated equally?

What are the results?

• Were results correctly analyzed and do you understand the results?

Is there external validity

?

Do the results apply to your patient and the population they represent?

Check population characteristics such as: age, sex.

Step 4: Applying to the individual

• What do the results mean on average?

• What do they mean for this individual?

What are the alternatives to EBM?

A dilemma

 You are very ill …

Which doctor do you want?

Life long learning

• The hardest conviction to get into the mind of a beginner is that the education upon which he is engaged is not … a medical course, but a life course, for which the work of a few years under teachers is but a preparation.

– Sir William Osler (1849-1919), from: The Student of Medicine

What is evidence-based medicine?

Evidence-based medicine is the integration of best

research evidence expertise

with

clinical

and

patient values

” -

Dave Sackett

Patient Concerns EBM Best research evidence Clinical Expertise

Pros and cons of EBP

EBP is a new name for an old practice. Literature has always guided clinical care. EBP uses processes and filters so that the decisions are made on strong evidence EBP is cook book. Decisions are solely made on evidence, down playing sound clinical judgment.

The use of evidence is one part of the process. Decisions are blended with individual clinical expertise, patient preference, and good evidence.

EBP is mindless application of population information to the treatment of one person.

The last step in EBP is to decide whether or not the information and results apply to the patient. Often there is not RCT or gold standard to address the clinical question Use the evidence pyramid and look for the next best level of evidence. Sometimes there is no evidence.

There can be difficulty in getting access to the evidence and in conducting effective searches to identify the best evidence.

Librarians can help identify the best resources and teach clinicians effective searching skills

When can evidence based practice hurt the patient?

• Poorly formed questions can lead to misdirection.

• Wrong diagnosis or questions researched, more clinical knowledge needed.

• Lack of explaining treatment, therapy to patient.

• Poor communication to patient.

• Rigidity in use of one arm of EBP.

• Use by insurers or providers in preventing care.