Art And Practice: Research Week 2 PDF

ART AND PRACTICE: RESEARCH WEEK 2 DR. MONIQUE AUCOIN ND MSc ANM 100 Week 13 QUESTION: WHAT DO WE DO WHEN WE HAVE CONFLICTING INFORMATION FROM DIFFERENT TYPES OF RESEARCH? OUTCOMES Identify and summarize the basic types of clinical epidemiological studies including: randomized controlled trials, coho...

ART AND PRACTICE: RESEARCH WEEK 2 DR. MONIQUE AUCOIN ND MSc ANM 100 Week 13 QUESTION: WHAT DO WE DO WHEN WE HAVE CONFLICTING INFORMATION FROM DIFFERENT TYPES OF RESEARCH? OUTCOMES Identify and summarize the basic types of clinical epidemiological studies including: randomized controlled trials, cohort studies, case-control studies, systematic reviews, case reports, n-of-1 studies, and whole systems research. Identify inherent strengths and weaknesses of each type of research design and how to assess quality based on their design and relevance to practice/individual patients and public health. RESEARCH STUDY METHODOLOGIES HIERARCHY OF EVIDENCE EXPERIMENTAL/INTERVENTION STUDIES DO Something to the patient, OBSERVE what happens Does the treatment change the likelihood of the outcome? Treatment TIME RANDOMIZED CONTROLLED TRIAL: CHARACTERISTICS Defined population (inclusion/exclusion criteria) 2(+) Groups: Treatment arm + Comparison arm Prospective: look forward in time Tx A TIME Tx B RANDOMIZED CONTROLLED TRIAL: CHARACTERISTICS Randomized: Equal chance of being assigned to the intervention or control group Control group: accounts for natural course of illness, placebo effect, confounding factors May have Blinding: minimize expectation effect RCT Use: **Best Design for confirming cause/effect** RANDOMIZED CONTROLLED TRIAL: CHARACTERISTICS Randomized: Equal chance of being assigned to the intervention or control group Control group: accounts for natural course of illness, placebo effect, confounding factors May have Blinding: minimize expectation effect RCT Use: **Best Design for confirming cause/effect** Treatment Control RANDOMIZATION For comparison to be useful, need to have truly RANDOM assignment to treatment/comparison -ex. people who visit clinic on weekday vs weekend; people who visit clinic A vs clinic B; judgement of clinician; flip of a coin; alternating -better: computer generated sequence, sequential numbered sealed opaque envelopes, 3rd party allocation Should describe HOW the randomization was done Should check to see that it worked, how similar were the groups? Selection Bias TABLE 1 Sample confounding factors: Age Gender Family history Comorbidities BMI Socioeconomic status Marital status Education Exercise Diet ANYTHING, known or unknown BLINDING Remove expectation Who was blind? -Participants (‘single blind’) -person delivering the intervention (‘double blind’) -person assessing the outcome (‘triple blind’) Should describe how it was achieved Bias in measurement of outcomes CLEARLY DEFINED POPULATION Participants are a SAMPLE of some population Inclusion/exclusion criteria help define Similar enough to your patient? (“generalizability”) -more or less ill? -different ethnicity or geographic location? -pregnancy, smoking, OCPs, non-English speaking, unable to read consent form, elderly, comorbidities, taking other medications Often excluded from clinical trials RECRUITMENT What was the method? Can influence the sample Ex. newspaper ad – people who read the newspaper and motivated to respond Ex. every person who presents at a clinic with a particular condition Selection Bias REPORTING OF RESULTS Power calculation Are the things they planned to measure (methods section) reported in the results section? Any missing data? Were p values reported? Reporting Bias COMPLIANCE Should be assessed Simple methods: Diary, pill count, phone calls, questioning Biological methods: blood/urine levels (costly) WITHDRAWALS How many participants enrolled, completed, dropped out (why?), analyzed Accounting for missing data: -Per-protocol analysis (analyse people in the intervention group that they completed) -Intention to treat analysis (analyse people in the intervention group that they were assigned to) WITHDRAWALS: RISK OF PERPROTOCOL ANALYSIS Mean skill level High EIP Skill Mean skill level Moderate EIP Skill Low EIP Skill High EIP Skill Extremely Hard Course Moderate EIP Skill Low EIP Skill Systematic factor impacting who drops out Other ex’s: side effect, acceptability, impact on outcome INTENTION TO TREAT ANALYSIS Analyze everyone in the group randomized, even if did not complete or ended up in the other group Techniques: last observation carried forward, statistical approaches Best way to minimize bias from drop outs Cautious, under-estimate of effect -Pre-Protocol: over-estimate INTENTION TO TREAT ANALYSIS High EIP Skill Mean skill level Moderate EIP Skill Low EIP Skill High EIP Skill Extremely Hard Course Moderate EIP SkillMean skill level Low EIP Skill RCT LIMITATIONS Difficult! (recruitment, funding, time) Sample may not be representative Not good for rare/distant outcomes Application to non-pill interventions can be challenging (control, blinding) Ethics of treating only some participants ASSESSING THE QUALITY OF RCTS Jadad Cochrane risk of bias –often used in SRs CASP checklist - https://casp-uk.net/casp-tools-checklists/ Assess quality of REPORTING: CONSORT CAM-specific reporting standards: Non-pharm CONSORT, Herbal Medicine CONSORT, REDHOT (homeopathy), STRICTA (acupuncture) JADAD SCALE Assess clinical trials Score from 0 to 5 2 points randomization 2 points blinding 1 point drop outs Stephen, H., Halpern, M. and Joanne, D., 2005. Jadad scale for reporting randomized controlled trials. OTHER KINDS OF INTERVENTION STUDIES Cross-over: everyone gets intervention AND comparison Pro: minimize confounder (participants are their own controls) Con: must be a chronic illness, treatment must washout Image source: Cochrane OTHER KINDS OF INTERVENTION STUDIES Preference (controlled, not randomized): choose between different arms (ex. Cancer survivors, pick MBT or Tai Chi) Open-label, Pre/Post: everyone gets the intervention (know it), assess changes before and after intervention Treatment TIME DESIGN A STUDY! Question: Dose a maternal diet deficient in B12 impact fetal brain development? appropriate study design? Clinical trial? Case report? Vandenbroucke JP. When are observational studies as credible as randomised trials?. The Lancet. 2004 May 22;363(9422):1728-31. OBSERVATIONAL STUDIES Exposure NOT controlled by the researcher They ask: Is there a relationship between a risk factor (or health factor) and an outcome (harm or benefit) Ex. Is high intake of blueberries associated with a lower risk of cancer? Is increased stress associated with an increased risk of a heart attack? Strength: Can study any question (harmful exposure, lack of a beneficial exposure) OBSERVATIONAL STUDIES TIME COHORT STUDY Compare Incidence Exposed CROSS-SECTIONAL STUDY TIME Un-exposed TIME Compare Prior Exposure Diseased TIME Non-Diseased CASE-CONTROL Compare Current Disease Status and Current Exposure COHORT STUDY Recruit the cohort (outcome is NOT present) Assess risk/health factors (creates a comparison grp) Follow over time See who develops the outcome “longitudinal” “prospective” TIME COHORT STUDY Exposed TIME Un-exposed Compare Incidence COHORT EXAMPLE: SATURATED FAT AND CVD Who developed CVD? Is there a difference between the groups? High sat fat diet -People without CVD -Ask about sat fat COHORT STUDY consumption TIME Exposed TIME Un-exposed Low sat fat diet Compare Incidence COHORT STUDIES Strengths Weaknesses Look at any exposure (even harm) Confident that exposure came before outcome Assignment to comparison grp is NOT random → risk of confounding Time consuming Inefficient for rare outcomes Assess multiple outcomes CASE-CONTROL Outcome is PRESENT at the beginning of the study Looks backwards in time for exposure (how much meat did you eat 10 years ago?) TIME Compare Prior Exposure Diseased TIME Non-Diseased CASE-CONTROL CASE CONTROL STUDIES Strengths Weaknesses Can look at rare outcomes Assignment to comparison grp is NOT random Faster (no waiting time, minimal loss of participants) Hard to assess temporality (ex. recall bias) Only assessing one outcome CASE CONTROL EXAMPLE Find people with AND without CVD -Is there a difference? TIME Compare Prior Exposure Diseased TIME Non-Diseased -Ask them to think about the past -high or low saturated fat diet? CASE-CONTROL CASE CONTROL STUDIES Strengths Weaknesses Can look at rare outcomes Assignment to comparison grp is NOT random Faster (no waiting time, minimal loss of participants) Hard to assess temporality (ex. recall bias) CROSS-SECTIONAL STUDIES Outcome is PRESENT at the beginning of the study CROSS-SECTIONAL STUDY Assess exposure and outcome at ONE time point Ex. Patients with CVD and healthy controls, ask about CURRENT meat intake Compare Current Disease Status and Current Exposure CROSS-SECTIONAL EXAMPLE CROSS-SECTIONAL STUDY Find people with AND without CVD Ask about sat fat in diet Is there a difference? Compare Current Disease Status and Current Exposure CROSS-SECTIONAL STUDIES Strengths Weaknesses Can study rare outcomes Faster Assignment to comparison grp is NOT random No recall bias No assessment of temporality (which came first?) Only assessing one outcome OBSERVATIONAL STUDIES: STRENGTHS Can study any question (harmful exposure, lack of a beneficial exposure) Can be less expensive or faster than intervention studies OBSERVATIONAL STUDIES: LIMITATIONS Not randomly assigned to exposure groups Investigate correlation, not necessarily causation APPRAISING THE QUALITY OF OBSERVATIONAL STUDIES Recruitment: Do the participants reflect the population of interest? Assessment of exposure: accurate? Subjective or objective? Validated? Consideration of confounding factors? Measurement or Classification Bias Selection Bias Generalizability of Findings Did the look for confounding factors? CASE REPORTS, CASE SERIES Report previously undocumented events (success, adverse reaction) May lead to further action Real patients and real clinical approaches BUT concerns about bias and generalizability N OF 1 STUDY Randomized, double blind, multiple crossover comparisons in an individual patient. “individualized RCT” - compare to self while taking the real treatment vs taking the comparison (ex. patient with hypertension: magnesium vs placebo or blood pressure medication) N OF 1 TRIAL DESIGN N OF 1 STRENGTHS Look at real world use of an intervention Allows for individualization, root-cause style treatment, complex health conditions, multi-modal treatments Can compare naturopathic and conventional treatments Could justify further research Consistent population (same person! Same genetics, family history, other risk factors) N OF 1 LIMITATIONS Doesn’t work if the condition is curable or self-limiting, must relapse in washout Findings may not be generalizable (low external validity) Ethics – need ethical approval, is it ethical to experiment in a clinical setting? High cost (manufacturing of placebo, administration of study with blinding) PRECLINICAL STUDIES In vitro: outside the body: cell lines, organs In vivo: in non-disease model: healthy human to study pharmacokinetics (absorption, elimination), animal models Base of the EBM hierarchy Basic knowledge to build on, allows to innovation, highly controlled, ‘ethical’, study mechanisms of action PRECLINICAL STRENGTHS Allow for creativity and innovation Background for future research in humans Investigate mechanism of action Study possible adverse events or interactions High level of control (ex. Exact intake of fiber in a mouse diet) Ethical (?) PRECLINICAL LIMITATION May not be clinically applicable to humans (lack generalizability) Highly controlled One isolated part of the story CONSIDER: Is pre-clinical evidence ‘sufficient’ enough to guiding clinical recommendations? Eg. In vitro anti-fungal effects of garlic are well known - does this mean that systemic fungal infections (highly dangerous) can/should be treated with garlic? At what dose? Eg. Soy phytoestrogen inhibits MCF-7 human breast cell growth in vitro - what does this mean for prevention/treatment of breast cancer? MIGHT CONSIDER Informed consent (document risks, benefits, level of evidence) Consider alternatives Monitor patient (response, safety) Alter treatment if needed SYNTHESIS RESEARCH Why? TIME!! Incorporate the results of individual studies together Draw bigger conclusions NARRATIVE REVIEWS Researcher combines some of the research on a topic Reports on the collection of evidence Often does NOT describe how they searched and how they decided to include certain studies High risk of bias – results often consistent with author’s hypothesis SYSTEMATIC REVIEWS Explicit and rigorous methods to: 1. Identify (2+ databases, specific inclusion/exclusion criteria) 2. Critically appraise 3. Synthesize (combine) Scientific investigation with pre-planned methodology Enormous effort to minimize bias META-ANALYSES Statistically combine the results of studies in a systematic review Ex. 5 studies with 20 participants → 1 study with 100 participants Visual representation of the studies (Forest Plot) SYSTEMATIC REVIEWS STRENGTHS Explicit and rigorous methods to: 1. Identify (2+ databases, specific inclusion/exclusion criteria) 2. Critically appraise 3. Synthesize (combine) Scientific investigation with pre-planned methodology Enormous effort to minimize bias Capture the big picture of evidence on a topic Meta-analysis allows for the creation of a larger sample size (helps with stats: stay tuned for next semester) SYSTEMATIC REVIEW LIMITATIONS Only as good as the available (findable) studies → publication bias, lack of research on a topic Can’t replace good clinical reasoning WHAT MAKES A STRONG SR? Clear question? Did they look for the right type of studies? -relevant to question, approp design (RCT if intervention) Comprehensive search? -databases, reference lists, unpublished studies, contact experts, non-English studies Assessment of study quality? WHOLE PRACTICE RESEARCH Need: Do the results of RCTs apply to real clinical practice of naturopathic medicine? Issues: RCT often use one intervention to treat one disease in a uniform patient population Naturopathic medicine: often complex interventions, prescribed in an individualized way, to patients with complex health conditions WHOLE PRACTICE/SYSTEMS RESEARCH Assess entire system of care vs individual treatments of modalities Ex. individualized acupuncture treatments vs testing 3 set acupuncture points Ex. Individualized homeopathy vs a single remedy Ex. Naturopathic medicine as a whole WSR TRIAL DESIGN Goal: accurately study what is actually done in the real world Modified RCT design: use an entire system of medicine vs individual therapy W H AT ’ S T H E METHODOLOGY? a) Systematic Review b) Intervention study c) Cohort Study d) Case-Control Study W H AT ’ S T H E METHODOLOGY? a) Systematic Review b) Intervention study c) Cohort Study d) Case-Control Study GROUP WORK WRAP UP AND QUESTIONS ANY THOUGHTS OR INSIGHTS OR N E W P E R S P E C T I V E F R O M TO D AY ’ S M AT E R I A L ?