N7000: INTRODUCTION TO EBP Week Seven: Experimental Studies Presented by: Corina Lelutiu-Weinberger, PhD Objectives 1. Define experimental (in particular randomized control trials) research studies 2. Compare/contrast to other types of research studies 3. Identify strengths/limitations of experimental studies 4. Discuss rapid appraisal of this type of research Meets 7000 Course Objectives: 4. Appraise the scientific merit and clinical relevance of research reports that use the following research designs: • Systematic reviews and meta-analysis • Experimental studies including randomized controlled trials • Observational (cohort and case control) studies • Cross sectional studies • Qualitative studies 5. Interpret research findings presented in tables, figures, and graphical displays. 7. Evaluate and engage in meaningful conversation regarding the appropriateness of scientific evidence for use in their clinical practice area. Circling Back Around… • You are working as an RN on in an oncology ambulatory surgery center. You begin to notice there are high preoperative anxiety levels in women undergoing breast surgery. Your institution recently hired a music therapist….and you wonder if music therapy may impact your patients positively. What could be considered a starting PICO question? PICO Ideas Which question is the most precise? 1. How does music impact anxiety? 2. What are effective methods for reducing anxiety in women with breast cancer? 3. Does music decrease levels of anxiety? 4. What is the impact of music therapy on women with breast cancer? 5. In women with breast cancer undergoing breast surgery, what is the impact of music therapy compared to no therapy on anxiety levels? And the answer is…. • In women with breast cancer undergoing breast surgery, what is the impact of music therapy compared to no therapy on anxiety levels? PICO And the search begins • Precise search terms • Limits (years; geographical area) • # and relevance of results Start with Most Relevant One But which elements in the article will be most informative? EXPERIMENTAL STUDIES: THE BASICS What is an experimental study? • Experimental studies aim to determine efficacy of an intervention (whether intended impact of intervention on outcome is statistically significant compared to control). • Can include randomization or not (RCT stronger than pre-post comparisons or open trials) What is a randomized control trial study? • RCTs are ranked high on the level of evidence pyramid • Includes intervention/treatment group vs. control group (or more) • Considered to be strongest methodology type used to test efficacy of treatment • Adaptive designs are gaining ground • Aims to establish cause and effect • Follows patients FORWARD in time Experimental Studies Experimental Study – Introduce an intervention or treatment Randomized – Assess its impact on one or more outcomes Yes No Randomized Controlled Trial (RCT) QuasiExperimental Screened (N = 14043) Screening Eligible, not participating (N = 847) Withdrew (n = 37) Eligible (N = 1893) Dropped (n = 84) Completed baseline assessment (N = 536) Baseline Excluded (n = 231) •Ineligible after rescreen (n = 17) •No sex risk (n = 136) •No HD risk (n = 41) •HIV positive (n = 13) •Incomplete testing (n = 16) •Inconsistent data (n = 8) Excluded (n = 2) Randomized to Comunică: n = 153 Ineligible (n = 12150) •Under age 16 (n = 113) •Not residing in Romania in the next 12 months (n = 830) •Not male gender (n = 1066) •Doesn’t have sex with men (n = 1869) •No CAS (n = 9452) •No HDD (n = 6911) •PrEP adherent (n = 413) •HIV positive (n = 898) •No mobile device (n = 155) •Hospitalized for mental illness (n = 184)* •Symptoms of psychosis (n = 946)* •Symptoms of mania (n = 787)* •Took antipsychotic or bipolar disorder medication (n = 542)* * As of 9/16/20 mental health screening questions are no longer part of eligibility criteria. Randomized to EAC: n = 152 Withdrew (n = 6) Withdrew (n = 2) 4-month follow-up Due 4M FU: n = 134 Retained: n = 120 (90%) Due 4M FU: n = 138 Retained: n = 124 (90%) 8-month follow-up Due 8M FU: n = 122 Retained: n = 106 (87%) Due 8M FU: n = 120 Retained: n = 101 (84%) 12-month follow-up Due 12M FU: n = 112 Retained: n = 104 (93%) Due 12M FU: n = 108 Retained: n = 95 (88%) Study completion (assessment + testing) n = 98 n = 88 Figure 1. Consort diagram. M = months; FU = follow-up CAS = condomless anal sex HDD = heavy drinking days Where Does It Fall? Where does it fall? Examples 1. Vitamin B12 supplementation in treating major depressive disorder: a randomized controlled trial 2. Efficacy of a Web-Based Intervention to Increase Uptake of Maternal Vaccines: An RCT 3. Effectiveness of Cranberry Capsules to Prevent Urinary Tract Infections in Vulnerable Older Persons: A Double-Blind Randomized Placebo-Controlled Trial in Long-Term Care Facilities CONSIDERATIONS FOR IMPLEMENTING AN INTERVENTION Extreme calorie intake Smoking Things we know are Cyanide harmful…not ethical Race Where one was raised Exposures in utero Things we can’t change about a person…not feasible Immunotherapy drug for cancer Outpatient drug treatment program Procedures for central line maintenance Things we can expose people to…but carefully Guiding research principles e.g. informed consent, favorable risk-benefit ratio (clinical equipoise) Important Terms A Note About Bias To review: • Bias is anything that distorts study results and comes from study methodology and results reporting. • Bias can occur at any point of the study Intervention Research Components (Minimize Bias) 1. Selection 2. Randomization 3. Measurement 4. Contamination 5. Reporting 6. Attrition Intervention Research Components 1. Selection a) Representativeness of sample b) Methods: probability, respondent driven sampling (RDS), convenience (includes snowballing), cluster c) Factors that affect sampling: • Location, time of day, method (flyer, social media, direct recruitment, clinician referral) Intervention Research Components 2. Randomization •Allocation Concealment • Can investigators or participants predict in advance who will be assigned to each group? •Blinding • Are participants and investigators adequately blinded? If not, is this likely to introduce bias? Randomization (continued) •Randomization in study conditions: • Group allocation by chance (at random) • Groups will be comparable participant-wise •When judging an intervention: • Is group allocation random? Does every participant have an equal and independent probability of being assigned to each group? • Stratification (balancing groups by characteristics): • Groups should ideally have equivalent age, gender, risk, etc, distributions Randomization (continued) Allocation vs. Blinding Concealment Allocation concealment occurs BEFORE the participant is enrolled in the study. Blinding occurs AFTER the participant is enrolled in the study Intervention Research Components 3. Measurement a) Conceptual (dictionary definition) Pain is defined as “physical suffering or discomfort caused by illness or injury” b) Operational (how is it actually measured) Pain is measured using FACES scale Operationalization 1. Which of these is clearly operationalized and why? a) The study measured mental health b) The study measured depression using the Beck’s Depression Inventory Validity 1. Internal- the degree in which changes to the dependent variable occur as a result of the independent variable 2. External- the extent to which results may be generalized to the population at large Take home points: - There is no perfect balance between the two - Interventions may be adapted Intervention Research Components (to minimize!) 4. Contamination Participants assigned to the non-intervention (control) arm are exposed/receive elements of the intervention. What does contamination affect? - validity Intervention Research Components (to minimize!) 4. Contamination (continued) A researcher intends to minimize cross-groups contamination in their intervention. Which of the strategies below would NOT prevent cross-group contamination? a) Not allow participants in one group to be exposed to materials from the other group b) Have different staff deliver the intervention and the control group materials c) Ensure that the two groups are exposed to their conditions for an equal amount of time Intervention Research Components 5. Reporting Selective Outcome Reporting • Do the investigators report all of their results? Only “desirable” results are reported - Null findings are typically under-reported or journals are less likely to accept manuscripts What are some implications of under-reporting? - treatments with low impact may be used Intervention Research Components (to minimize!) 6. Attrition The portion of the sample that dropped out of the study. - 20% attrition is reasonable - Power calculations - Important for analyses (did people at higher risk drop out?) - Conduct analyses to see if there were any differences between retained and lost participants - Be transparent when reporting limitations and interpreting results Variables: Beyond Independent and Dependent Confounding variables- a variable related to both your independent variables and affects your dependent variable(s) • It must be correlated with the independent variable. • May or may not be a causal relationship • It must be causally related to the dependent variable. • How can you manage them? Examples of Odds Ratios Associations of Sexual Minority Stigma and Alcohol/ Drug Use at Last Sexual Encounter “For the three substance-related outcomes, a one standard deviation increase in stigma was associated with a 19% increase in the odds of sex under the influence of alcohol at the last sexual encounter, a 27% increase in the odds of sex under the influence of cannabis at the last sexual encounter, and a 49% increase in the odds of sex under the influence of illicit drugs at the last sexual encounter. Table 2. Regression models for sexual behavior under the influence and HIV testing awareness predicted by sexual orientation stigma (n = 2,087). Age Missing covariates (ref. = no) Missing stigma (ref. = no) University education (ref. = basic) Employed (ref. = unemployed) Bisexual orientation (ref. = gay) City dweller (ref. = small city/town) Had a steady partner (ref. = no) Sexual orientation stigma (z-score) Last sex: Under the influence of alcohol B AOR 95% CI -0.02 0.98** [0.97, 0.99] Last sex: Under the influence of cannabis B AOR 95% CI -0.01 0.99 [0.97, 1.01] Last sex: Under the influence of club drugs B AOR 95% CI -0.01 0.99 [0.97, 1.01] Knowing where to get an HIV test B AOR 95% CI 0.04 1.04** [1.01, 1.06] 0.21 1.24 [-0.07, 0.49] 0.52 1.68* [1.05, 2.69] 0.16 1.18 [0.71, 1.95] -0.52 0.59* [0.39, 0.90] 1.06 2.88*** [0.47, 1.65] 0.46 1.58 [0.60, 4.17] 0.66 1.93 [0.75, 4.94] -1.02 0.36** [0.19, 0.68] -0.13 0.88 [0.72, 1.07] -0.43 0.65* [0.45, 0.96] 0.04 1.04 [0.71, 1.53] 0.29 1.33 [0.93, 1.92] -0.29 0.75* [0.59, 0.96] -0.07 0.93 [0.59, 1.47] -0.32 0.73 [0.45, 1.19] 0.03 1.03 [0.67, 1.58] 0.44 1.55*** [1.22, 1.98] 0.55 1.74** [1.14, 2.64] 0.83 2.30*** [1.52, 3.47] -0.25 0.78 [0.52, 1.17] 0.24 1.27* [1.03, 1.55] 0.31 1.37 [0.91, 2.05] 0.23 1.25 [0.82, 1.92] 0.40 1.50* [1.06, 2.12] -0.26 0.77* [0.63, 0.95] -0.34 0.71 [0.49, 1.04] -0.28 0.76 [0.52, 1.11] 0.23 1.26 [0.88, 1.79] 0.18 1.19*** [1.07, 1.33] 0.24 1.27* [1.03, 1.56] 0.40 1.49*** [1.22, 1.82] 0.23 1.26* [1.01, 1.59] Notes. N = 2087. * p < 0.05; ** p < 0.01; *** p < 0.001. All models were adjusted for demographic characteristics significantly associated with sexual orientation stigma. B = unadjusted coefficient; AOR = Adjusted coefficient 32 Variables: Beyond Independent and Dependent Extraneous variables- not a focus of your investigation but can affect results. Aspects you are not manipulating or measuring but that can affect your findings: • Neighborhood dilapidation (can affect asthma data) • Diet (can affect fertility treatment outcomes) • Can you give us examples? Variables: Beyond Independent and Dependent • How can you manage extraneous variables? - Include in your models (“adjust” or “control” for them) - Publicly available data (census, etc) - If cannot be measured • • results interpretation and/or limitations section mention (+ future directions) Extraneous vs. Confounding Variables https://www.scribbr.com/methodology/extraneous-variables/ Strengths of Experimental Studies • Randomization • helps to minimize selection bias • Blinding of study information from participants and research team • can reduce demand characteristics/social desirability and experimenter effects biases Strengths of Experimental Studies (continued) • Dedicated groups: treatment and control group (or more) - only type of study to determine causality • Have specific inclusion and exclusion sample criteria which leads to… • Higher internal validity Weaknesses of Experimental Studies • Placebo effect • Ethics • Protocol rigidity • implementation science • Threats of extraneous factors EXPERIMENTAL STUDIES: CRITICAL APPRAISAL Critical Appraisal To Review: Critical appraisal is the “systematic unbiased, careful examination of all aspects of studies to judge their strengths, limitations, trustworthiness, meaning and applicability to practice” (Burns & Grove, 2021) Critical Appraisal Critical appraisal is “one of the most valuable skills that clinicians can possess in today’s healthcare environment. Distinguishing the best evidence from unreliable evidence and unbiased evidence from biased evidence lies at the root of the impact the clinicals’ actions will have in producing their intended outcomes” (Melnyk & Fineout-Overholt, 2019, p. 109) Critical Appraisal: Deeper Dive 1. Title and Abstract - Does the title of the article indicate the type of study that was conducted? - Is the abstract comprehensive (i.e. includes study aims, design, sample, intervention, results and implications)? Critical Appraisal 2. Introduction: Problem Statement and Purpose Statement - Are the significance and background of the problem described? - Is the purpose statement clearly written? - Do the authors describe how their findings will contribute to science, practice and/or policy? Critical Appraisal 3. Review of Literature - Were previous studies described? - How old were studies in the review of literature? - Did researchers critically describe studies in their review of literature (e.g., pointed to poor or strong sampling procedures, limitations of methodologies)? - Did the researchers point to the gap in the knowledge they aim to address (e.g., whether assertiveness in healthcare utilization may be increased with peer navigation)? - Were there research questions and/or hypotheses? Critical Appraisal 4. Research design - What is the specific study design (RCT, cluster randomized controlled trial, open pilot)? - Was the treatment or intervention described in detail? - If there was a comparison made, what was/were the comparison group(s) and are they sufficiently described? - If more than one study group was used, how were participants assigned to their groups? - Were extraneous variables identified? Critical Appraisal 5. Population, sample, setting - Are inclusion/exclusion criteria clearly defined? - What type of sampling method was used? - What is the sample size? - What was the attrition rate? - Was IRB approval obtained, was informed consent conducted? - What is the study setting? Critical Appraisal 6. Variables - Were variables identified and defined both conceptually (assertiveness) and operationally (Rathus Assertiveness Scale)? - Independent variable clearly defined (impact of peer navigation intervention vs. reading infographics on assertiveness)? - Dependent variable clearly defined (blood pressure)? - Are demographic variables clear (was the sample on the older side)? Critical Appraisal 7. Measurement - What were the measurement instruments? (Validated scales or researcher-developed? Was permission for use needed and gained?) - What type of measurement instrument was used (Likert scale? Physiologic measurement? EMR data?) - Was the reliability of instrument used provided? - Was validity of the scale or instrument used provided? Critical Appraisal 8. Data management and statistical analyses - How were the data collected, scales calculated? - What statistical tests were used? - Were analyses done to test all proposed hypotheses? - Was the level of significance provided? 9. Results - Were the results clearly reported and based on hypotheses? - Was anything left out? Critical Appraisal 10. Discussion - How were results interpreted by researchers? - Were findings expected? - How were surprising findings interpreted? - Did the researchers interpret their findings in relation/comparison to existing literature (confirm, extend, disprove) 9. Limitations - Were study limitations identified (any, enough)? Critical Appraisal Critical Appraisal