Module 1 Flashcards
(178 cards)
1
Q
Case-Control Study
A
Subjects recruited based on disease status»_space; Exposure Status
2
Q
- CLINICAL QUESTION: What happened?
- Rare diseases
- Illnesses with long latency periods
- Evaluation of a wide range of potential etiologic exposure
A
Case-Control Study
3
Q
- means a group of subjects followed over a period of time
Main Objectives : - To describe the incidence of certain outcomes over time (DESCRIPTIVE)
- To analyze associations between risk factors and those outcomes (ANALYTICAL)
A
Cohort Study
4
Q
Prospective Cohort Study
A
Recruitment of Subjects based on exposure status»_space;Prospective» Disease Status
5
Q
- CLINICAL QUESTION: What will happen?
- Sample of subjects without the outcome of interest
- Predictor variables measured
- Subjects followed over a period of time
- Most effective way to establish the temporal sequence of predictor and outcome variables
A
Prospective Cohort Study
6
Q
Retrospective Cohort Study
A
(Historical Cohort)
- Sample of subjects with the outcome of interest
- similar to the prospective cohort study except that baseline measurements, follow-up, and outcomes all happened in the past
- Only possible if there is adequate data on the risk factors and outcome
7
Q
Retrospective Cohort Study
A
Selection of Subjects based on exposure status»_space;Records review» Disease Status
8
Q
- Exposure status and Disease status are measured at one point in time
- Useful for chronic illnesses (gradual onset, long duration)
- Prevalence studies
- Less costly than cohort studies
A
Cross-Sectional Studies
9
Q
- A Systematic Investigation
- Directly involves a person / group of people or human materials
- Researchers interact directly with human subjects or collects identifiable private information
- Includes research development, testing, and evaluation
A
Clinical Research
10
Q
Types of Clinical Research
A
- Patient-oriented research
- Epidemiological and behavioral studies
- Outcomes and health services research
11
Q
- Research in disease, therapeutic interventions, clinical trials, and development of new biotechnologies
- Most vulnerable to ethical problems because human subjects are the basis of the experiments
A
Patient-oriented research
12
Q
Humans as Experimental Subjects
A
- Participants in clinical research undergo risks, often without any direct benefit
- They help advance science for the benefit of others
- The experimental design and implementation must conform to the highest ethical standards
13
Q
EVIDENCE-BASED MEDICINE (EBM)
A
INTEGRATION OF 1. Best research evidence 2. Clinical expertise 3. Patient values IN CLINICAL DECISIONS
14
Q
WHY IS EBM IMPORTANT?
A
- Information overload
- 30-60% of published research articles have some form of bias
- Review of literature is one of the first steps to doing a research study
- Inculcation of “RESEARCH ATTITUDE”
15
Q
THE EBM CYCLE
A
COMPONENTS OF THE CYCLE A. Asking the Question B. Searching the Literature C. Appraising the Evidence D. Integrating the Data E. Making a Decision
16
Q
RESEARCH QUESTION (PICOM components)
A
PICOM components
Population to be studied Intervention or exposure = Independent variable Comparisons to be made (control) Outcome of interest = Dependent variable Methodologic (study design)
17
Q
RESEARCH QUESTION (PIO components)
A
PIO components
Population to be studied
Intervention or exposure
Outcome of interest = Dependent variable
18
Q
“To evaluate, to judge the value/worth”
A
APPRAISING THE EVIDENCE
19
Q
COMPONENTS OF CRITICAL APPRAISAL
A
- Is the study valid?
- VALIDITY / LACK OF BIAS - What are the results?
- SIZE AND PRECISION OF EFFECT - Will the results help me in caring for my patients?
- APPLICABILITY AND IMPACT
20
Q
Validity vs Precision
A
Validity = Accuracy - The “TRUTH” - Lack of significant bias - The PRIME requirement of any study NOT VALID= W/ SYSTEMATIC ERROR = BIASED Precision = Reliability - “Repeatability” - Consistency - NOT PRECISE = W/ RANDOM ERROR = LOW SAMPLE SIZE
21
Q
USERS’ GUIDES FOR ARTICLE ON THERAPY (Validity)
A
VALIDITY
- Was the assignment of patients to treatments randomized?
- Was follow up complete?
- Were patients analyzed in the groups to which they were randomized?
- Were patients, health workers, and study personnel “blind” to treatment?
- Were the groups similar at the start of the trial?
- Aside from the experimental intervention, were the groups treated equally?
22
Q
USERS’ GUIDES FOR ARTICLE ON THERAPY (Results)
A
RESULTS
- How large was the treatment effect?
- How precise was the estimate of the treatment effect?
23
Q
USERS’ GUIDES FOR ARTICLE ON THERAPY (Applicability)
A
APPLICABILITY
- Can the results be applied to my patient care?
- Were all clinically important outcomes considered?
- Are the likely treatment benefits worth the potential harms and costs?
24
Q
TYPES OF INTEGRATIVE STUDIES
A
- Review
- Overview
- Systematic Review / Meta-analysis
- Clinical Practice Guidelines
25
- A detailed and organized, step by step search for all the material available on a topic
- A well-structured literature search is the most effective and efficient way to locate sound evidence on the subject you are researching.
Literature Search
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Fast becoming a basic skill
- journal report / research requirements
- clinical/medical case report
- medical audits
- evaluating new technologies, drugs
- thesis and research presentations
- practice of evidence based medicine
Literature Search
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The electronic search: A NEW approach
- Time-saving
- It is possible to search any word you wish
- Combine terms to make complex searches
- Can yield thousands of sources with one click of a button
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Efficient Search
- Avoid searches that are TOO BROAD and UNFOCUSED
| - Avoid searches that are TOO NARROW and thus missing key articles
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Steps in Conducting the Literature Search
STEP 1: Develop an initial search strategy
STEP 1A - Phrase the question as precisely as possible
STEP 1B - Identify key concepts in the question phrased
STEP 1C - Broaden each key concept to account for differences in terminology
STEP 1D - Narrow down the yield of the search by using the “intersect” of the broadened concepts
STEP 2 - Run the search and modify if necessary to obtain an optimal strategy
STEP 3 - Save the search strategy
STEP 4 - Download the yielded articles
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STEP 1: Develop an initial search strategy
| STEP 1A: Phrase the question as precisely as possible
A well‐built clinical question
P ‐ patient description
I ‐ intervention and comparative intervention
O ‐ clinical outcome of interest (mortality, cure, relief, QOL, etc)
M ‐ methodology used
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Methodologic Filters
- Randomized controlled trial
- Meta-analysis
- Clinical trial
- Review
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- Standardized dictionary of medical terms
| - Obviates the need for long search strategies marked by an endless list of synonyms
Medical Subject Heading (MeSH) Searches
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When we broaden the key concepts, we face the danger of retrieving hundreds of thousands of articles
STEP 1C: Broaden each key concept to account for differences in terminology
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- Boolean logic is the way to put terms together in a search by using AND, OR, NOT.
- Allows you to join terms together, widen a search or exclude terms from your search results
- It allows a more precise method of locating information
- Use UPPERCASE when using boolean operators
The Boolean Logic
35
(The Boolean Logic)
- Narrows your search by making sure that all your terms show up in an article.
- Example: handwash* AND compliance* AND nurs* would bring back articles that relate to handwashing and compliance and nursing - including all the truncated (asterisk is used for truncation) forms of the words.
AND
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(The Boolean Logic)
- Broadens your search by allowing any of the terms to show up in an article; it is also useful for linking together synonyms.
- Example: handwash* OR hand wash* OR hand hygiene would bring back articles with handwashing and its synonyms.
OR
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(The Boolean Logic)
- Narrows your search by eliminating a term from your search.
- Example: handwash* NOT alcohol gel would bring back articles on handwashing, but not articles on alcohol gels used in handwashing
NOT
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WHAT IS PUBMED?
- Search interface from the U.S. National Library of Medicine (NLM).
- Covers the fields of medicine, nursing, dentistry, pharmacy, and others areas of the life sciences.
- Provides access to over 21 million citations in MEDLINE, PreMEDLINE, and other related databases
- Citations from the 1950s to the present are searchable in PubMed
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Run the search and modify if necessary, to obtain an optimal strategy.
- You may use filters like the age bracket, sex (if necessary), publication type, language, etc to further limit the search
- NOTE: Do not use filters/limits too early in the search because you might miss relevant articles
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Features of Pubmed Engine
Using filters
- Chose the study design
- Chose the age group of your patients
- Limit the search to a particular language
- Limit the search to human studies
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- will help you if you are looking for a specific phrase or title. You need to put the phrase in quotation marks. By using quotation marks, the phrase is considered as one word
- Example: “blood pressure,” “three months
Phrase searching
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- Around half the diseases in the world have no treatment
- Understanding how the body works and how diseases progress, and finding cures, vaccines or treatments, can take many years of painstaking work using a wide range of research techniques
- There is overwhelming scientific consensus worldwide that some research using animals is still essential for medical progress
Research Using Animals
43
Categories of animal research
- As model systems for the investigation of phenomena and processes which cannot be studied directly
* Most animals studies
- To investigate a problem specific to the particular species
* Field studies: behavioral and ecological adaptations of animal species
* Taxonomic relationships among species
* Captive studies: Physiological or behavioral processes form an important part of the adaptations of one or more species
44
Why research using animals?
- Animals are employed as part of a range of scientific techniques
* ONLY used for parts of research where no other techniques can deliver the answer
- A living body is an extraordinarily complex system
* Not all experiments may be carried out in a test tube
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Why research using animals?
- Lab animals have organs and body systems similar to humans
- Susceptible to the same diseases as humans
* For extrapolation
- Short life span >> allowing study of life cycles
- Allows precise control over the animals’ environment (light, temperature, ventilation)
* Ensures health
* Keeps experimental variables minimum
- Healthy, well cared-for, adequately housed animals are necessary to produce accurate research results
46
Claude Bernard, Father of Physiology:
- “Experiments on animals are entirely conclusive for the toxicology and hygiene of man. The effects of these substances are the same on man as on animals, save for differences in degree.”
- Bernard established animal experimentation as part of the standard scientific method
47
Animals used in biomedical research help us with the ff:
- Understand how our bodies work
- Find cures and treatments for diseases
- Test new drugs for safety
- Evaluate medical procedures before they are used on people
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Cruelty to animals and the 3Rs campaign
(1) Replacementof animals with non-living models
(2) Reductionin the use of animals
(3) Refinementof animal use practices
49
Is it morally right to use animals for research?
- Most people believe that in order to achieve medical progress that will save and improve lives, perhaps millions of lives, limited and very strictly regulated animal use is justified
- Animal research benefits animals too: more than half the drugs used by vets were developed originally for human medicine
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- Veterinarians with specialized training in laboratory animal medicine are an integral part of a medical research team
- As part of this research group, veterinarians assure the humane treatment of animals and provide medical and surgical support throughout research studies
- Emergency veterinary care for research animals is available on a 24-hour basis
Veterinary care
51
- Although humans are masters over lesser creatures, dominion over them and over themselves is only a stewardship for which human beings remain responsible to the one Lord
- God has called human beings to use their own initiative and originality in completing His work of creation
Stewardship
52
- Research and experiments, with all their risks involved, are necessary
- BUT, we must proceed with reverence for the persons and the environment at risk
Stewardship
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WMA Statement on Animal Use in Biomedical Research (Preamble) (1)
1. Biomedical research is essential to the health and well-being of our society. Advances in biomedical research have dramatically improved the quality and prolonged the duration of life throughout the world. However, the ability of the scientific community to continue its efforts to improve personal and public health is being threatened by a movement to eliminate the use of animals in biomedical research. This movement is spearheaded by groups of radical animal rights activists whose views are considered to be far outside mainstream public attitudes and whose tactics range from sophisticated lobbying, fund-raising, propaganda and misinformation campaigns to violent attacks on biomedical research facilities and individual scientists. These violent attacks are carried out by a relatively small number of activists compared with those who use peaceful means of protest, but they have profound and wide-ranging effects.
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WMA Statement on Animal Use in Biomedical Research (Preamble) (2)
2. The magnitude of violent animal rights activities is staggering, and these activities take place in many different parts of the world. Various animal rights groups have claimed responsibility for the bombing of cars, institutions, stores, and the private homes of researchers.
55
WMA Statement on Animal Use in Biomedical Research (Preamble) (3)
3. Animal rights violence has had a chilling effect on the scientific community internationally. Scientists, research organizations, and universities have been intimidated into altering or even terminating important research efforts that depend on the use of animals. Laboratories have been forced to divert thousands of research dollars for the purchase of sophisticated security equipment. Young people who might otherwise pursue a career in biomedical research are turning their sights to alternative professions.
56
WMA Statement on Animal Use in Biomedical Research (Preamble) (4)
4. Despite the efforts of many groups striving to protect biomedical research from radical animal activism, the response to the animal rights movement has been fragmented, under-funded, and primarily defensive. Many groups within the biomedical community are hesitant to take a public stand about animal activism because of fear of reprisal. As a result, the research establishment has been backed into a defensive posture. Its motivations are questioned, and the need for using animals in research is repeatedly challenged.
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WMA Statement on Animal Use in Biomedical Research (Preamble) (5)
5. While properly designed and executed research involving animals is necessary to enhance the medical care of all persons, we recognize also that humane treatment of research animals must be ensured. Appropriate training for all research personnel should be prescribed and adequate veterinary care should be available. Experiments must comply with any rules or regulations promulgated to govern humane handling, housing, care, treatment and transportation of animals.
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WMA Statement on Animal Use in Biomedical Research (Preamble) (6)
6. International medical and scientific organizations must develop a stronger and more cohesive campaign to counter the growing threat to public health posed by animal activists. Leadership and coordination must be provided. In addition, there must be a clear understanding of the rights of animals who are part of medical research, and the obligations of those who undertake it.
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WMA Statement on Animal Use in Biomedical Research: The World Medical Association therefore affirms the following principles: (1-2)
1. Animal use in biomedical research is essential for continued medical progress.
2. The WMA Declaration of Helsinki requires that biomedical research involving human subjects should be based, where appropriate, on animal experimentation, but also requires that the welfare of animals used for research be respected.
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WMA Statement on Animal Use in Biomedical Research: The World Medical Association therefore affirms the following principles: (3-4)
3. Humane treatment of animals used in biomedical research is essential and research facilities should be required to comply with all guiding principles for humane treatment. Education about these principles should be provided to all researchers in training.
4. Animals should only be used in biomedical research when it is clear that their use is required to achieve an important outcome, and where no other feasible method is available.
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WMA Statement on Animal Use in Biomedical Research: The World Medical Association therefore affirms the following principles: (5-7)
5. Duplication of animal experiments should not occur unless scientifically justified.
6. The use of animals for the futile testing of cosmetic products and their ingredients, alcohol and tobacco should not be supported.
7. Although rights to free speech should not be compromised, the anarchistic element among animal right activists should be condemned.
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WMA Statement on Animal Use in Biomedical Research: The World Medical Association therefore affirms the following principles: (8-9)
8. The use of threats, intimidation, violence, and personal harassment of scientists and their families should be condemned internationally.
9. A maximum coordinated effort from international law enforcement agencies should be sought to protect researchers and research facilities from activities of a terrorist nature.
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(Animal Contributions to Research)
- Vaccine for leprosy
Armadillos
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(Animal Contributions to Research)
- Studies for AIDS, eye and ear disorders, and the nervous system
Cats
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(Animal Contributions to Research)
- Studies on middle ear infections and hearing loss
Chinchillas
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(Animal Contributions to Research)
- Coronary bypass surgery; artificial heart valve insertion; pacemaker implantation; hip and other joint replacement surgery
Dogs
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(Animal Contributions to Research)
- Viral diseases such as influenza
Ferrets
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(Animal Contributions to Research)
- Studies of vision, liver cancer, bacterial diseases, temperature regulation, and skin tumors
Fish
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(Animal Contributions to Research)
- Nutritional studies such as vitamin C deficiency
Guinea Pigs
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(Animal Contributions to Research)
- Study of motor coordination diseases such as syphilis and Parkinson's disease
Lobsters
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(Animal Contributions to Research)
- Studies of cancer, aging, AIDS, immunology, and genetics; embryo transfer techniques in humans and domestic and endanger animal species
Mice
72
(Animal Contributions to Research)
- Treatments for polio and Rh disease; studies of HIV and AIDS, cancer, heart disease, neurological disorders, and infectious diseases such as malaria
Nonhuman Primates
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(Animal Contributions to Research)
- Studies of the Central nervous system, immune system and bacterial endocarditis
Opossums
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(Animal Contributions to Research)
- Study of coronary heart diseases
Pigeons
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(Animal Contributions to Research)
- Burn treatments; development of the CAT scan; human heart valve replacements
Pigs
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(Animal Contributions to Research)
- Corneal transplants; drugs that lower blood cholesterol and help stop the development of hardening of the arteries
Rabbits
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(Animal Contributions to Research)
- Studies to find treatment for paralysis caused by nerve damage; product safety tests; causes of some cancers; effects of nutrition on aging; understanding tissue rejection following transplant surgery
Rats
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(Animal Contributions to Research)
- Development of the arteriovenous shunt and testing of a device that assists lung functions in infants soon after birth.
Sheep
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(Animal Contributions to Research)
- Studies of the short- and long-term memory
Slugs
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(Animal Contributions to Research)
- Liver cancer and hepatitis B
Woodchucks
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(Animal used in research)
- Diphtheria vaccine
- Typhoid Fever vaccine
- Aging and Alzheimer research
- Cancer and nutrition
- Muscular dystrophy
Rats, Mice and other Rodents
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(Animal used in research)
- Kidney disease research
- Bone research
- Skin transplantation
- Penicillin as an antibiotic
- Polio vaccine
Rats, Mice and other Rodents
83
(Animal used in research)
- Measles vaccine
- Regulation of cholesterol
- Hormonal treatment of cancer
- Breast cancer research
Rats, Mice and other Rodents
84
(Animal used in research)
- Small pox vaccine
- Organ transplants
- Diabetes research
- Development of computer assisted tomography (CAT) scan
Cattle and Swine
85
(Animal used in research)
- Heart disease and circulation research
- Arthritis and osteoporosis research
- Cure for hand, foot and moth disease
- Cure for hog cholera
Cattle and Swine
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(Animal used in research)
- Rabies vaccine
- First cataract surgery
- Corneal transplants
- Link between virus and cancer
- Acquired immunity research
Rabbits
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(Animal used in research)
- Cholesterol studies
- Effects of aging
- Muscular disease
- Product safety testing
- Drug metabolism research
Rabbits
88
(Animal used in research)
- Cardiovascular research
- CPR techniques
- Vision research (glaucoma, cataracts)
- Digestion research
- Therapeutic use of insulin
Dogs
89
(Animal used in research)
- Bone marrow transplantation
- Suture and grafting of blood vessels
- Respiration research
- Anemia therapy
- Cholesterol and heart disease research
Dogs
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(Animal used in research)
- Tetanus vaccine
- Malaria research
- Cure of beriberi
- Use of either as an anesthetic
- Edema treatment
- Importance of vitamins A, C and D
Frogs, Fish, Reptiles and Birds
91
(Animal used in research)
- Cell chemistry research
- Neurobiological studies
- Liver cancer research
- Diabetes research
- Coronary heart disease
Frogs, Fish, Reptiles and Birds
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(Animal used in research)
- Polio vaccine
- Rubella vaccine
- Hepatitis B vaccine
- Cure for yellow fever
- Discovery of Rhesus (Rh) factor in blood
Nonhuman Primates
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(Animal used in research)
- Treatment for Parkinson's disease symptoms
- AIDS research
- Measles research
- Anesthesia research
- Periodontal disease research
Nonhuman Primates
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- Fundamental Skill: Asking well-built clinical questions
- Questions are relevant to patients’ problems
- Questions are phrased in ways that direct your search for relevant and precise answers
Asking Focused Questions
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Elements of well-built questions
P - Patient or Problem
I - Intervention (treatment,cause, prognostic factor etc…)
C - Comparison Intervention (if necessary)
O - Outcome
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Elements of well-built questions (PICO) Patient/Problem; Intervention
Tips for Building
Patient or Problem
- Start with patient, ask “How would I describe a group of patients similar to mine?” Balance precision with brevity
Intervention
- Ask “Which main intervention am I considering?” Be specific
97
Elements of well-built questions (PICO) Comparison; Outcome
Comparison
- Ask “What is the main alternative with the intervention?” Again, be specific
Outcome
- Ask “What can I hope to accomplish?” or “What could this exposure really affect?” Again, be specific
98
Finding the Evidence (Treatment; Diagnosis)
Use terms in the PICO for your literature search strategy
1. Treatment: P, I, O
2. Diagnosis: P, I, C, O
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Finding the Evidence (Treatment; Diagnosis)
3. Harm: P, I/E, O
4. Prognosis: P, I/E, O
5. Prevalence: P, O or P, O - T
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EBM CYCLE COMPONENTS
```
A. Asking the Question
B. Searching the Literature
C. Appraising the Evidence
D. Integrating the Data
E. Making a Decision
```
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To integrate the best available research evidence with the physician’s expertise and patient values to make better informed decisions in health care
Evidence Based Medicine
102
Formulating answerable clinical questions
- Types of questions
- Structure of reasonable questions – PICO-T
- The “best”research type depends on the question type
103
What are the … outcomes (PO)
- Patients
- Outcomes?
- Qualitative Research
- Example: RA – what is the most important symptom? Prevalence Prognosis
104
The best evidence depends on the type of clinical question 1
1. What are the phenomena/thoughts? (FREQUENCY)
- Observation (Qualitative Research)
2. What is the frequency of the problem? (DIAGNOSIS)
- Random (or consecutive) sample
105
The best evidence depends on the type of clinical question 2
3. Who will get the problem? (PROGNOSIS)
- Follow-up of inception cohort
4. How to we alleviate the problem? (THERAPY)
- Randomized controlled trial
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- A heuristic that clinicians and patients can use to answer clinical questions quickly
- Rules of thumb that helps us make decisions in real environments
- The levels cover the entire range of clinical questions: prevalence, therapeutic effects, common harms, rare harms, accuracy of diagnostic tests,
OCEBM Levels of Evidence
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How common is the problem? (PREVALENCE STUDY)
```
Level 1: Random surveys or censuses
Level 2: Systematic Review of Surveys
Level 3: Non-random sample
Level 4: Case-series
Level 5: n/a
```
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Is this diagnostic or monitoring test accurate?
(DIAGNOSIS STUDY)
(Level 1-2)
Level 1: Systematic Reviews of Cross-sectional Studies
- with consistently applied reference standards and blinding
Level 2: Individual cross sectional studies with consistently applied reference standards and blinding
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Is this diagnostic or monitoring test accurate?
| DIAGNOSIS STUDY) (Level 3-5
Level 3: Non-consecutive studies, or studies without consistently applied reference standards
Level 4: Case-control
- Poor or non-independent reference standard
Level 5: Mechanism based reasoning
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What will happen if we do not add a therapy? (COHORT STUDY)
Level 1: Systematic review of inception cohort studies
Level 2: Inception cohort studies
Level 3: Cohort study or control arm of randomized trials
Level 4: Case-series
- Case-control
- Poor quality prognostic cohort studies
Level 5: n/a
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Does this intervention help?
| TREATMENT BENEFITS
Level 1: Systematic reviews of randomized trials or n-of-1 trials
Level 2: Randomized trials or observational study with dramatic effect
Level 3: Non-randomized controlled cohort / follow-up study
Level 4: Case-series
- Case-control
- Historically controlled studies
Level 5: Mechanism-based reasoning
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What are the COMMON Harms? (TREATMENT HARMS) (Level 1-2)
Level 1: Systematic reviews of randomized trials, systematic reviews of nested case-control studies, n-of-1 trial with patient you are raising the question about, or observational study with dramatic effect
Level 2: Individual randomized trial or (exceptionally) observational study with dramatic effect
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What are the COMMON Harms? (TREATMENT HARMS) (Level 3-5)
Level 3: Non-randomized controlled cohort
Provided there are sufficient numbers to rule out a commmon harm
Level 4: Case-series
- Case control
- Historically controlled cohort studies
Level 5: Mechanism-based reasoning
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What are the Rare harms?
(TREATMENT HARMS)
(Level 1-2)
Level 1: Systematic review of randomized trials or n-of-1 trials
Level 2: Randomized trial or (exceptionally) observational study with dramatic effect
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What are the Rare harms?
(TREATMENT HARMS)
(Level 3-5)
Level 3: Non-randomized controlled cohort
- Provided there are sufficient numbers to rule out a commmon harm
Level 4: Case-series
- Case Control
- Historically controlled studies
Level 5: Mechanism-based reasoning
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Is this (early detection) screening test worthwhile?
Level 1: Systematic review of randomized trials
Level 2: Randomized trial
Level 3: Non-randomized controlled cohort / follow-up study
Level 4: Case-series
- Case control
- Historically controlled cohort studies
Level 5: Mechanism based reasoning
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An __ is a clinical trial in which a single patient is the entire trial, a single case study. A trial in which random allocation can be used to determine the order in which an experimental and a control intervention are given to a patient
N of 1 trial
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Heterogeneity may be the rule and not the outlier. It may not be proper to group patients with different genetic makeups.
Human genome project:
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- The proper study of me is me! trial with one subject: n of 1 trial
Cancer trials:
120
How common is the
| problem?
Level 1: Local and current random sample surveys (or censuses)
Level 2: Systematic review of surveys
that allow matching to local
circumstances**
Level 3: Local non-random sample**
Level 4: Case-series**
Level 5: n/a
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Systematic approach to clinical problem solving which allows the integration of the best available research evidence with clinical expertise and patient values
Evidence–Based Medicine
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The EBM Triad
- Patient Values and Expectations
- Individual Clinical Expertise
- Best External Evidence
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- Involves a process of lifelong self directed learning in which caring for patients creates the need for important information about clinical and other health care issues
- Most important reason for practising EBM is to improve quality of care through the identification and promotion of practices that work, and the elimination of those that are ineffective or harmful
Evidence–Based Medicine
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Three Skills of EBM
1. Acquiring the evidence
2. Appraising the evidence
3. Applying the evidence
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Five Step EBM Model
1. Converting information needs into answerable questions
2. Finding the best evidence with which to answer the questions
3. Critically appraising the evidence for its validity and usefulness
4. Applying the results of the appraisal into clinical practice
5. Evaluating performance
126
Skills and Steps of EBM
Appraise
Appraise directness >>> Appraise validity >>> Appraise result
Apply
Assess applicability >>> Individualize results
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Systematic process used to identify the strengths and weaknesses of a research article in order to assess the usefulness and validity of research findings
Critical Appraisal
128
10 questions to ask in critical
| appraisal of articles (1-5)
1. Is the study question relevant?
2. Does the study add anything new?
3. What type of research question is being asked?
4. Was the study design appropriate for the research
question?
5. Did the study methods address the most important
potential sources of bias?
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10 questions to ask in critical
| appraisal of articles (6-10)
6. Was the study performed according to the original
protocol?
7. Does the study test a stated hypothesis?
8. Were the statistical analyses performed correctly?
9. Do the data justify the conclusions?
10. Are there any conflicts of interest?
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Study should addresses an important topic and adds to what is already known about that subject
Is the study question relevant?
131
Most fundamental task of critical appraisal is to identify the specific research question that an article addresses/ Identify PICO
What type of research question is being asked?
132
- Specific research question determines the optimal study design
- Studies that answer questions about effectiveness have a well-established hierarchy of study designs based on the degree to which the design protects against bias
Was the study design appropriate for the research question?
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Was the study design appropriate for the research question?
| Hierarchy of study Designs
1. Systematic reviews
2. Randomized Controlled Trials
3. Cohort Studies
4. Case-control studies
5. Case Series, Case Reports
6. Editorials, Expert Opinion
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However, in some circumstances, RCTs are either not feasible or considered ethically inappropriate
Was the study design appropriate for the research question?
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Was the study design appropriate for the research question? (1-3)
1. Aetiology: the causes of disease and their model of operation (Case-control or cohort study)
2. Diagnosis: signs, symptoms or tests for diagnosing a disorder (Diagnostic validation study)
3. Prognosis: the probable course of disease over time (Inception cohort study)
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Was the study design appropriate for the research question? (4-6)
4. Therapy: selection of effective treatments which meet your patient's values (Randomized-control trial)
5. Cost-effectiveness: is one intervention more cost-effective than another (Economic evaluation)
6. Quality of life: what will be the quality of life of the patient? (Qualitative Study)
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- Presence of bias means the results of a study have deviated from the truth
- Two general types of bias
1. Random error
2. Systematic bias
Did the study methods address the most important potential sources of bias?
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- Attributed to chance
| - Does not influence the results in any particular direction, but it will affect the precision of the study
Random error
139
- Results in the overestimation or underestimation of the “truth”
- Arise from the way in which the study is conducted, be it how study participants were selected, how data was collected, or through the researchers’ analysis or interpretation.
Systematic bias
140
- Different study designs are prone to varying sources of systematic bias
- Once the study design of a given article has been identified, it is recommended that clinicians use one of the available design-specific critical-appraisal checklists to decide whether the study in question is of high quality
Did the study methods address the most important potential sources of bias?
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- Deviations from the planned protocol can affect the validity or relevance of a study.
Ex: Failure to recruit the planned number of participants (Reduces the extent to which the results of the study can be generalized to real-world situations, but also reduces the power of the study to demonstrate significant findings)
- Changes to the inclusion and exclusion criteria
Was the study performed in line with the original protocol?
142
- Deviations from the planned protocol can affect the validity or relevance of a study.
Ex:
*Variation in the provided treatments or interventions
*Changes to the employed techniques or technologies
*Changes to the duration of follow-up
Was the study performed in line with the original protocol?
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Hypothesis
- Clear statement of what the investigators expect the study to find
- States the research question in a form that can be tested and refuted
Null hypothesis
- States that the findings of a study are no different to those that would have been expected to occur by chance
Does the study test a stated hypothesis?
144
(Does the study test a stated hypothesis?)
- Involves calculating the probability of achieving the observed results if the null hypothesis were true
- If this probability is low (conventionally less than 1:20 or P
Statistical hypothesis testing
145
- Study hypotheses must crucially be identified a priori
* If the study investigates the statistical significance of associations that were not prespecified in the original hypothesis (posthoc analysis), such analyses are prone to false- positive findings
- Check that all data relevant to the stated study objectives have been reported, and that selected outcomes have not been omitted
Does the study test a stated hypothesis?
146
- All quantitative research articles should include a segment within their ‘Method’ section that explains the tools used in the statistical analysis and the rationale for this approach, which should be written in terms that are appropriate for the journal’s readership
Were the statistical analyses performed correctly?
147
- Patients who are lost in follow-up and missing data should be clearly identified in the ‘Results’ section. The approach to dealing with the missing data and the statistical techniques that have been applied should be specified
- Original data should be presented in such a way that readers can check the statistical accuracy of the paper
Were the statistical analyses performed correctly?
148
- Conclusions that the authors present should be reasonable on the basis of the accumulated data
Do the data justify the conclusions?
149
(Do the data justify the conclusions?)
What to watch out for:
- Sometimes there is overemphasis on statistically significant findings that invoke differences that are too small to be of clinical value
- Authors may generalized their findings to broader groups of patients or contexts than was reasonable given their study sample
150
- occur when personal factors have the potential to influence professional roles or responsibilities
- Mechanism for dealing with potential conflicts of interest is open disclosure
Are there any conflicts of interest?
151
- Identification of a potential conflict of interest is not synonymous with having an actual conflict of interest or poor research practice
- Potential conflicts of interest are extremely common, and the most important questions are whether they have been recognized and how they have been dealt with
Are there any conflicts of interest?
152
- The researchers might state specifically that the sponsoring agency had no input into the research protocol, data analysis or interpretation of the findings
Are there any conflicts of interest?
153
Overview of Critical Appraisal Guides
1. Appraise Directness/Relevance
- Does the study provide a direct enough answer to your clinical question in terms of type of patients (P), exposure/ intervention (E) and outcome (O)?
2. Appraise Validity*
3. Appraise Results*
4. Appraise Applicability
- Biologic and Socio – Economic issues that may affect applicability of treatment?
5. Individualizing the results*
*where appraisal guides usually differs for each type of article
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Risk of Disease with Drug A (Rt)
Rt = A/(A+B)
155
Risk of Disease without Drug A (Rc)
Rc = C/(C+D)
156
Relative Risk
RR = Rt/Rc
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Absolute Risk Reduction (ARR)
ARR = Rc-Rt
158
Relative Risk Reduction (RRR)
RRR = ARR(absolute risk reduction)/Rc
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Number Needed to Treat (NNT)
NNT = 1/ARR
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(Overview of Critical Appraisal on Therapy) - Appraise Validity (1-4)
1. Were patients randomly assigned to treatment groups?
- Look for the word "randomize", "randomly allocated" in methods.
2. Was allocation concealed?
- Look for strategies such as use of opaque envelopes, randomization by third party, or randomization by computer.
3. Were baseline characteristics similar at the start of the trial?
- Look for a comparison in tables or in the text.
4. Were patients blinded to treatment assignment?
- Look for blinding strategies such as use of a placebo. This may not always be feasible or necessary.
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(Overview of Critical Appraisal on Therapy) - Appraise Validity (5-8)
5. Were caregivers blinded to treatment assignment?
- Look for blinding strategies such as use of a placebo. This may not always be feasible or necessary.
6. Were outcome assessors blinded to treatment assignment?
- Look for strategies to withhold information regarding patient assignment.
7. Were all patients analyzed in the groups to which they were originally randomized?
- Look for the term “intention-to-treat” under the planned analysis.
8. Was follow-up rate adequate?
- Drop-outs should be stated explicitly in a paper. If not, compare number recruited with number of patients analyzed at end of study.
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(Overview of Critical Appraisal on Therapy) - Appraise Results
1. How large was the effect of treatment?
- For dichotomous outcomes –look for hazards ratios, relative risk, relative risk reduction, or absolute risk reduction (also known as risk difference). For continuous outcomes – look for the mean difference.
2. How precise was the estimate of the treatment effect?
- Look for 95% confidence intervals around the estimates of treatment effect mentioned above.
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(Overview of Critical Appraisal on Therapy) - Individualizing the Results
1. What is the likely effect of the treatment on your individual patient? (Estimate the individualized NNT for your patient)
- Using the patient’s baseline risk for the outcome (based on clinical presentation) and the risk reduction (based on the study), one can estimate the individualized absolute risk reduction
2. Would you offer the treatment to your patients?
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Overview of Critical Appraisal on Systematic Review -Appraise Validity (1-2)
1. Were the criteria for inclusion of studies appropriate?
- Look for inclusion criteria in the methodology section.
2. Was the search for eligible studies thorough?
- Look for specification of a computerized search, hand searches of relevant journals, personal communication with known researchers on a topic (including drug companies), and other methods to search for unpublished articles.
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Overview of Critical Appraisal on Systematic Review -Appraise Validity (3-4)
3. Was the validity of the included studies assessed?
- Look for a quality scale for studies, or qualitative descriptions of the studies included.
4. Were the assessments of the studies reproducible?
- At least two authors should be evaluating the quality of included studies.
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Overview of Critical Appraisal on Systematic Review - Appraise Result
1. What are the overall results of the review?
- Results may be summarized in tables or graphs (eg – forest plots).
2. Were the results similar from study to study?
- Look for tests for heterogeneity. If present, authors should explain where heterogeneity is coming from, and how they plan to deal with it.
3. How precise were the results?
- Look for overall 95% confidence intervals if results were combined statistically.
167
Overview of Critical Appraisal on Systematic Review - Individualizing the Results
1. What is the implication of study findings on your individual patient? (Estimate the individualized NNTs for your patient)
2. Would you offer the treatment to your patients?
168
Overview of Critical Appraisal on Diagnosis - Appraise Validity
1. Was the reference standard an acceptable one?
- Look for how authors define presence or absence of disease in the study population.
2. Was the reference standard interpreted independently from the test in question?
- Look for terms such as “independent” or “blind” to describe how evaluations were made. In general, blinding will require a prospective study.
169
Overview of Critical Appraisal on Diagnosis - Appraise Results
1. What likelihood ratios were associated with the range of possible test results?
- Look for likelihood ratios. If these are not reported, they can be derived from sensitivity and specificity.
170
Overview of Critical Appraisal on Diagnosis - Individualizing the Results
1. How will the test results affect the probability of disease in your patient? (Estimate the individualized post-test probability of your patient)
- Using the patient’s pre-test probability (based on clinical presentation) and the likelihood ratio (based on the study), one can estimate the patient-specific post-test probability.
2. Is this test useful for your patient?
171
Overview of Critical Appraisal on Harm - Appraise Validity (1-2)
1. Did exposure precede outcome in the study?
- Look for the exposure and outcome. Determine whether the exposure was established first. Usually if outcomes were established first, they would indicate that the outcome was already present and that they determined the exposure through interview, records review or the use of a questionnaire.
2. Were the patient groups being compared sufficiently similar with respect to baseline characteristics? If not, were statistical adjustments made?
- Look for characteristics of the comparison groups. These are usually shown in a table.
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Overview of Critical Appraisal on Harm - Appraise Validity (3-5)
3. Were unbiased criteria used to determine exposure in all patients?
- Look for a description of the method used to ascertain exposure, usually under patients and methods.
4. Were unbiased criteria used to detect outcome in all patients?
- Look for a description of the method used to ascertain outcome, usually under the methods section.
5. Was follow-up rate adequate?
- Drop-outs should be stated explicitly in a paper. If not, compare number recruited with number of patients analyzed at end of study.
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Overview of Critical Appraisal on Harm - Appraise Results
1. How strong is the association between exposure and outcome?
- For case-control studies, look for odds ratios. For cohorts and RCT’s relative risks are more often reported.
2. How precise is the estimate of the risk?
- Look for 95% confidence intervals around the estimates of causal association as mentioned above.
174
Overview of Critical Appraisal on Harm - Individualizing the Results
1. What is the likely effect of the exposure on the risk of your individual patient? (Estimate the individualized NNT/NNH for your patient)
- Using the patient's baseline risk for the outcome (based on clinical presentation) and the odds ratio (based on the study), one can estimate the individualized absolute risk increase.
2. Would you ask the patient to avoid the exposure?
175
Overview of Critical Appraisal on Prognosis - Appraise Validity
1. Was the sample of patients’ representative?
- Look for a sampling strategy, or, if disease is rare, look for some assurance that consecutive patients were recruited.
2. Were patients (or subgroups of patients) sufficiently homogeneous with respect to prognostic factors?
- Inclusion criteria should be very specific, and, when appropriate, homogeneous patient subgroups should be sub-analyzed.
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Overview of Critical Appraisal on Prognosis - Appraise Validity
3. Were objective and unbiased outcome criteria used?
- Look for description of method to ascertain outcome.
4. Was follow-up rate adequate?
- Drop-outs should be stated explicitly in a paper. If not, compare number recruited with number of patients analyzed at end of study.
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Overview of Critical Appraisal on Prognosis - Appraise Result
1. How likely are the outcomes over time?
- Look for event rates, survival rates, relative risk, or Kaplan-Mayer survival curves.
2. How precise are the estimates of likelihood?
- Look for 95% confidence intervals around the estimates of causal association as mentioned above.
178
Overview of Critical Appraisal on Prognosis - Individualizing the Results
1. What is the estimate of prognosis in your patient?
| - Using the patient's clinical characteristics, use the study to estimate a patient-specific prognosis.
