Drug information and Guidelines

Question 1

AGREE instrument and Bandolier

Answer 1

tools for evaluating guidelines

Question 2

Agency for Healthcare Research and Quality (AHRQ)

Answer 2

catalog of guidelines, tools to give you ability to compare guidelines by structured elements (see handout), they NO longer write guidelines

Question 3

How do you find guidelines?

Answer 3

#PubMed
#AHRQ guidelines.gov
#Cochrane collaboration
#National Institute for Clinical Excellence (British)

Question 4

Sources of Oncology based Guidelines

Answer 4

#NCCN (both EBM and consensus)
#ASCO (EBM)
#ONS (specific to RN, both EBM and CBM)
#MASCC (both) (Multinational Assoc of Supportive Care in Cancer
#ASBMT (EBM)
#Int'l Assoc for Hospice and Palliative Care Medicine
#ESMO (European)
#IDSA
#Pediatric Oncology Group of Ontario

Question 5

Meta-analyses

Answer 5

#statistics on aggregate information
#systematic review
#way to combine results of multiple trials and to reanalyze
#use rigorous methods to prevent bias and erroneous results "garbage in, garbage out" even MORE important here

Question 6

why would you do a meta-analysis?

Answer 6

#clear clinical question (very impt!!)
#address sample size and beta error issues (particularly common in CA studies is too small sample size)
#varying, inconsistent results in current trials
#address subgroup issues (problematic because sufficient study power DOES NOT apply to subgroups)

Question 7

what studies do you want to include in a meta-analysis?

Answer 7

SIMILAR
#study design 
#allocation
#patient selection
#therapies
#consistent data points 
#outcomes

Question 8

How do you identify studies for meta-analysis?

Answer 8

Find everything!!
#search at least 2 databases (ie. PubMed gold std, Web of Science, Embase, Cochrane, Medline, etc.)
#search ascendancy (references that your identified article listed) and descendancy (references that cited your identified article POST publication)
#unpublished sources (manufacture, FDA, abstracts, US trial registry)
#language bias (often limited to English language)

Question 9

meta-analysis Search terms

Answer 9

#MeSH searching and text word searching
#limits (common RCTs only)
#date range of search

Question 10

How are studies selected for inclusion in Meta-analysis?

Answer 10

#NEED TO WORRY ABOUT both study selection bias and patient selection bias
#quality assessment

Question 11

Study assessment for meta-analysis

Answer 11

#multiple reviewers assess all trials
#disagreement resolved by consensus
#consistent methodology to review and abstract all trials
#investigators contacted for missing data
#some meta-analysis studies use criteria to assess quality of studies (many formulas available, often assess allocation)

Question 12

does it make sense to combine studies for meta-analysis?

Answer 12

#patients with similar dz states, interventions, outcomes, study designs
#tools to assess: forest plots and heterogeneity

Question 13

how do you assess for bias in meta-analysis studies?

Answer 13

#selection of pts, allocation
#interventions: similar tx
#interventions: competing tx
#confounding
#measurement and observer error
#outcomes used
#compliance, attrition
#duration of tx

Question 14

forest plots (qualitative) to assess heterogeneity of meta-analysis

Answer 14

Are point estimates highly variable?
Do confidence intervals overlap?
BOX: point estimate (ie. relative risk)
size of box= relative sample size, line whiskers =CI (larger the line, smaller the sample size)->looking to see that boxes are pretty close to show qualitative heterogeneity, looking for outliers. if wild heterogeneity look to studies to dig in and understand

Question 15

Cochran Q statistic (quantitative) to assess heterogeneity of meta-analysis

Answer 15

based on chi squared statistic, p value less than 0.1 or 0.05 = significant heterogeneity
hypothesis = NOT heterogeneity

Question 16

Cochran Q statistic (quantitative) to assess heterogeneity of meta-analysis - LIMITATIONS (2pts)

Answer 16

underpowered for studies with few pts, #overpowered for large sample sizes.

Question 17

I^2 statistic (quantitative) to assess heterogeneity of meta-analysis

Answer 17

variability across studies due to treatment effect
#0% variability due to chance alone
#0-25% low hetero
#25-50% moderate hetero
#>50% high
#PUSH to included CI's for this stat. (ie. 0-62% would not be ideal but may be reported now as 0%)

Question 18

fixed effects model - meta-analysis

Answer 18

#assumes one true value
#considers sample variation with studies (each pt has SAME weighted value)
#use if LOW hetero

Question 19

random effects model - meta-analysis

Answer 19

#assumes a range of effects
#cosiders variation with study AND between studies (pt's could have DIFFERENT weighted values)
#use if MOD/HIGH hetero

Question 20

what is common method to decide which effects model to use? - meta-analysis

Answer 20

#Primarily use fixed effects UNLESS significant hetero THEN Secondarily use random effects
#can use different effects model for different outcomes within the SAME study

Question 21

“leave one out procedure” used in random effects - meta-analysis

Answer 21

assess effect of individual studies by leaving each study out and assessing the results

Question 22

subgroups analysis- meta-analysis

Answer 22

#step back - does this make sense?
#particularly subject to CONFOUNDING BIAS
#fishing expeditions (p value penalty)
#subgroups may NOT reflect randomization
#adjust for multiple comparisons
#alpha, beta, power

Question 23

sensitivity analysis- meta-analysis

Answer 23

#evaluate the impact of different decisions made in the conduct of the study (ie. if both fixed and random effects examined if they give similar answer than sensitivity is robust)
#different study designs such as RCT and epidimiology = similar outcomes

Question 24

funnel plot. What does this assess?

Answer 24

#plot effect size vs sample size
#used to assess publication and selection bias
#if studies evenly distributed under the funnel - NO publication bias
#if studies on ONE side - publication bias
people are not excited about publishing neutral studies

Question 25

example limitations - meta-analysis

Answer 25

using only published data, no quality control on original records, heterogeneity in trial design, differences in chemo regimens, relatively small # of trials and pts

Question 26

data mutations - meta-analysis

Answer 26

#strategy to be able to calculate NNT off of nominal data
#may mean LOSS of data
#change continuous data to nominal date (ie. pts who had at least 50% reduction in pain, pts whose bp was in nml range)

Question 27

Tools for evaluating meta-analysis

Answer 27

provides checklists for what to look for
#CASP: critical appraisal skills program
#Bandolier
#PRISMA Statement

Question 28

SUPPLEMENTAL MATERIALS TO REVIEW NOT ON THE VIDEO

Answer 28

PubMed searching (subheadings, etc.), other literature searching sites (EMBASE, Cochrane), internet website notes (NCI toxicity criteria, FDA drug and biologic sections (2 sections)), resources for evaluating clinical guidelines, National Guidelines Clearinghouse (different parameters), HIPAA

Question 29

HIPAA alphabet- PHI

Answer 29

protected health information

Question 30

HIPAA alphabet- covered entity

Answer 30

or

Question 31

HIPAA alphabet- BAA

Answer 31

business associates agreement

Question 32

HIPAA alphabet- TPHA

Answer 32

treatment, payment, and healthcare operations - exclusion principles

Question 33

HIPAA alphabet- HITECH

Answer 33

amendment that has increased fines, risk, and exposure to organizations

Question 34

Research and HIPAA

Answer 34

#quality improvement vs research
#IRB and HIPPA
#PHI disclosures without authorization (reporting an adverse event to the FDA, legally required reporting)
#violations and penalties (REVIEW THIS)