Post on 21-Jan-2018
Carlos A. Cuello Garcia MD, PhD(c) Health Research Methodology Program Department of Clinical Epidemiology and Biostatistics
Guideline development
Levels of evidence and the GRADE approach
DISCLOSURE• currently working at
MacGRADE centre & Cochrane GRADEing group
• Cochrane author
• I have received support from the WAO for travel / meetings
• no other COIs related to this talk
GRADEingMethods
OUTLINE
• what are clinical practice guidelines?
• why should we use them?
• what are recommendations and levels of
evidence?
• how to interpret a CPG recommendation?
ATOPIC DERMATITIS
EASY! PIMECROLIMUS
EASY! PIMECROLIMUS
WHAT ABOUT CANCER REPORTED?
WE BETTER STAY WITH TOPICAL
CORTICOSTEROIDS
WE BETTER STAY WITH TOPICAL
CORTICOSTEROIDS
PIMECROLIMUS IS BETTER THAN TCS
???
PIMECROLIMUS OR TOPICAL CORTICOSTEROIDS?
Meanwhile, at the Ministry of Health…
CLINICAL PRACTICE GUIDELINES
๏ statements that include recommendations
intended to optimize patient care that are
informed by a systematic review of evidence
and an assessment of the benefits and harms
of alternative care options.
IOM · AHRQ 2011
CLINICAL RECOMMENDATION
EVIDENCE
PATIENT VALUES
ACCEPTA-BILITY
BENEFITS VS HARMS COSTS
IN PATIENTS (CLINICAL) GUIDELINES
DECISION
EVIDENCE
PATIENT VALUES
ACCEPTA-BILITY
BENEFITS VS HARMS FEASIBILITY
EQUITY RESOURCE USE
IN PUBLIC HEALTH GUIDELINES
guidelines we can trust๏ Based on a
systematic review ofthe existing evidence
1
guidelines we can trust๏ Developed by a
knowledgeable,multidisciplinarypanel of experts andrepresentatives fromkey affected groups
2
guidelines we can trust๏ Considers important
patient subgroupsand patient
preferences
3
guidelines we can trust๏ Based on an explicit
and transparentprocess thatminimizes distortions,biases, and conflictsof interest
4
guidelines we can trust๏ Provides a clear
explanation of the logicalrelationships betweenalternative care options andhealth outcomes, andprovide ratings of both thequality of evidence and thestrength of
recommendations
5
guidelines we can trust๏ It is revised as
appropriate whenimportant newevidence warrantsmodifications ofrecommendations.
6
CLINICAL RECOMMENDATION
or DECISION
EVIDENCE
PATIENT VALUES
ACCEPTA-BILITY
BENEFITS VS HARMS FEASIBILITY
EQUITY RESOURCE USE
CLINICAL RECOMMENDATION
or DECISION
EVIDENCE
RESEARCH GENERATION
PUBLISHING
RESEARCH GENERATION
PUBLISHING
RESEARCH GENERATION
PUBLISHING
RESEARCH GENERATION
PUBLISHING
systematic reviews
clinical practice guidelines
RESEARCH GENERATION
PUBLISHING
systematic reviews
clinical practice guidelines
RESEARCH GENERATION
PUBLISHING
systematic reviews
clinical practice guidelines
CHALLENGES AHEAD
why we need trustworthy clinical practice guidelines?
๏ Every year $100 billion dollars are invested in biomedical research
๏ Only 10% is used to test treatments
Chalmers 2009
$
๏ only half of researchers use a systematic review that has been previously done on their topic
Chalmers I, Glasziou P. Lancet 2009;374:86-9 Cooper NJ, et al Clin Trials 2005;2:260–4.
50%
๏ only half of researchers use adequate tools to ensure the quality of their work
Chalmers I, Glasziou P. Lancet 2009;374:86-9 Cooper NJ, et al Clin Trials 2005;2:260–4.
CONSORT
๏ not all research is registered, reported, or published…
Cressey D. Secrets of trial data revealed. Nature. 2013 Oct 10;502(7470):154-5
RESEARCH GENERATION
and many times we overlook research priorities and patient important outcomes
Chalmers I, Glasziou P. Lancet 2009;374:86-9 Cooper NJ, et al Clin Trials 2005;2:260–4.
100 participants
parachute placebo
100 participants
36.5 (2.1) 36.7 (1.9)
4.3 (1.2) 6.1(1.3)
25 (3) 22(2.4)
Temp ºC –mean (SD)
Fear scale –mean (IQR)
Serum adrenaline (mcg/dL) – mean
(SD)
parachute placebo
100 participants
36.5 (2.1) 36.7 (1.9)
4.3 (1.2) 6.1(1.3)
25 (3) 22(2.4)
Temp ºC –mean (SD)
Fear scale –mean (IQR)
Serum adrenaline (mcg/dL) – mean
(SD)
p=0.00001
parachute placebo
antiarrhythmicsPatients with MI
ecainide flecainide placebo
↓ ↓
↑↑
arrhythmias
death ??
Epstein AE, et al. JAMA 1993
outcomes Patients with asthma
nitrous oxide placebo
O2 sat
FEV1
Length of hospital stay
Death
so, do you recommend..?
so, do you recommend..?
๏ pimecrolimus or topicalcorticosteroids for atopic dermatitis?
so, do you recommend..?
๏ pimecrolimus or topicalcorticosteroids for atopic dermatitis?
๏ nitrous oxide for severe asthma?
so, do you recommend..?
๏ pimecrolimus or topicalcorticosteroids for atopic dermatitis?
๏ nitrous oxide for severe asthma?๏ probiotics for allergy prevention?
so, do you recommend..?
๏ pimecrolimus or topicalcorticosteroids for atopic dermatitis?
๏ nitrous oxide for severe asthma?๏ probiotics for allergy prevention?๏ epinephrine for anaphylactic shock?
expert recommendations
cross-sectional
case series, case reports
case-control
cohort
Randomized trial
Systematic review
CTFPHE 1979
expert recommendations
cross-sectional
case series, case reports
case-control
cohort
Randomized trial
Systematic review
CTFPHE 1979
I good
II fair
III poor
EVIDENCE
expert recommendations
cross-sectional
case series, case reports
case-control
cohort
Randomized trial
Systematic review
CTFPHE 1979
I good
II fair
III poor
EVIDENCE
A
B
C
RECOMMENDATION
D
I want to jump from this airplane
do you recommend a parachute?
Grading of Recommendations Assessment, Development and Evaluation
expert recommendations
cross-sectional case series
case-control
cohort
RCT
cross-sectional case series
case-control
cohort
RCT RCT
Observational
experience is not evidence,
it’s a tool
By default...
cross-sectional case series
case-control
cohort
RCT RCT
Observational
HIGH QUALITY
LOW QUALITY
QUALITY OF EVIDENCE
๏ You can also call it: ๏ certainty of evidence ๏ confidence in the estimates
Balshem H, et al. GRADE guidelines: 3. Rating the quality of evidence. J Clin Epidemiol. 2011;64(4):401-6
QUALITY OF EVIDENCE
Balshem H, et al. GRADE guidelines: 3. Rating the quality of evidence. J Clin Epidemiol. 2011;64(4):401-6
SYSTEMATIC REVIEWCLINICAL PRACTICE
GUIDELINE
the extent of our confidence that the estimates of the effect are correct
the extent of our confidence that the estimates of the effect are adequate to support a particular decision or recommendation
QUALITY OF EVIDENCE
HIGH We are very confident that the true effect lies close to that of the estimate of the effect
We are moderately confident in the effect estimate: The true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially
different
Our confidence in the effect estimate is limited: The true effect may be substantially different from the
estimate of the effect
We have very little confidence in the effect estimate: The true is likely to be substantially different from the
estimate of effect
MODERATE
LOW
VERY LOW
how is the quality (confidence) of the evidence determined?
what would make you loose confidence?
๏ Overall, probiotics reduced the risk of eczema in infants when given to their pregnant mothers
๏ RR=0.72 (95% CI 0.61 to 0.85)
๏ 3’509 participants, 15 trials
QUALITY OF EVIDENCE
risk of bias
STUDY 1 STUDY 2 STUDY 3
QUALITY OF EVIDENCE
inconsistency
risk of bias
STUDY 1 STUDY 2 STUDY 3
QUALITY OF EVIDENCE
inconsistency
indirectn
ess
P I C O
?
risk of bias
STUDY 1 STUDY 2 STUDY 3
QUALITY OF EVIDENCE
inconsistency
indirectn
ess
P I C O
?
imprecision
risk of bias
STUDY 1 STUDY 2 STUDY 3
QUALITY OF EVIDENCE
inconsistency
indirectn
ess
P I C O
?
imprecision
publication biasrisk of bias
STUDY 1 STUDY 2 STUDY 3
By default...
cross-sectional case series, etc.
case-control
cohort
RCT RCT
Observational
HIGH QUALITY
LOW QUALITY
By default...
RCT
Observational
HIGH QUALITY
LOW QUALITY
RCT
HIGH
MODERATE
LOW
VERY LOW
QUALITY OF EVIDENCE
RCT
HIGH
MODERATE
LOW
VERY LOW
QUALITY OF EVIDENCErisk of bias
HIGH
MODERATE
LOW
VERY LOW
QUALITY OF EVIDENCE
RCT
risk of bias
HIGH
MODERATE
LOW
VERY LOW
QUALITY OF EVIDENCE
RCT
risk of bias
inconsistency
HIGH
MODERATE
LOW
VERY LOW
QUALITY OF EVIDENCE
RCT
risk of bias
inconsistency
imprecision
HIGH
MODERATE
LOW
VERY LOW
QUALITY OF EVIDENCE
RCT
risk of bias
inconsistency
imprecision
indirectn
ess
HIGH
MODERATE
LOW
VERY LOW
QUALITY OF EVIDENCE
RCT
risk of bias
inconsistency
imprecision
indirectn
ess
publication bias
VERY LOW
QUALITY OF EVIDENCE
RCT
risk of bias
inconsistency
imprecision
indirectn
ess
publication bias
OBSERVATIONAL
HIGH
MODERATE
LOW
VERY LOW
QUALITY OF EVIDENCE
OBSERVATIONAL
HIGH
MODERATE
LOW
VERY LOW
QUALITY OF EVIDENCE
strong association
HIGH
MODERATE
LOW
VERY LOW
QUALITY OF EVIDENCE
OBSERVATIONAL
strong association
dose response
HIGH
MODERATE
LOW
VERY LOW
QUALITY OF EVIDENCE
OBSERVATIONAL
strong association
dose response
opposing residual
confounding
HIGH
QUALITY OF EVIDENCE
OBSERVATIONAL
strong association
dose response
opposing residual
confounding
from evidence to recommendations
Quality of evidence
Strength of a recommendation
the extent of our confidence that the estimates of an effect are adequate to support a particular decision or recommendation
the extent to which one can be confident that the desirable consequences of an intervention outweigh its undesirable consequences
NO
YES
YES
NO
stre
ngth
of a
rec
omm
enda
tion
direction of a recommendation
for
against
NO
YES
YES
NO
stre
ngth
of a
rec
omm
enda
tion
direction of a recommendation
for
against
STRONG
NO
YES
YES
NO
stre
ngth
of a
rec
omm
enda
tion
direction of a recommendation
for
against
CONDITIONAL
STRONG
patients
clinicians
policy makers
Most individuals in this situation would want
the recommended course of action, and
only a small proportion would not
Most individuals should receive the intervention.
Adherence to this recommendation could
be used as a quality criterion or
performance indicator
The recommendation can be adopted as
policy in most situations.
STRONG CONDITIONAL
The majority of individuals in this situation would want the suggested course of action, but many would not
Different choices will be appropriate for individual patients. Must help each patient arrive at a management decision consistent with his or her values and preferences.
Policy making will require substantial debate and involvement of various stakeholders.
FRAMEWORKS
evidence to recommendation
just 4 columns & conclusions
CRITERIA
CRITERIA
Problem
Quality of evidence
Benefits & harms
Values
Resource use
Equity
Acceptability
Feasibility
CRITERIA
Problem
Quality of evidence
Benefits & harms
Values
Resource use
Equity
Acceptability
Feasibility
JUDGEMENTSRESEARCH EVIDENCE
ADDITIONAL INFORMATION
CRITERIA
Problem
Quality of evidence
Benefits & harms
Values
Resource use
Equity
Acceptability
Feasibility
JUDGEMENTSRESEARCH EVIDENCE
ADDITIONAL INFORMATION
what is to be considered?
CRITERIA
Problem
Quality of evidence
Benefits & harms
Values
Resource use
Equity
Acceptability
Feasibility
JUDGEMENTSRESEARCH EVIDENCE
ADDITIONAL INFORMATION
what do we consider about
it?
CRITERIA
Problem
Quality of evidence
Benefits & harms
Values
Resource use
Equity
Acceptability
Feasibility
JUDGEMENTSRESEARCH EVIDENCE
ADDITIONAL INFORMATION
what do we consider about
it?
�����
CRITERIA
Problem
Quality of evidence
Benefits & harms
Values
Resource use
Equity
Acceptability
Feasibility
JUDGEMENTSRESEARCH EVIDENCE
ADDITIONAL INFORMATION
based on what evidence?
CONCLUSIONS
Balance of consequences
Decision /recommendation
Justification
Implementation considerations
Monitoring
Evaluation
Research priorities
example
Explanations Prepared by: Holger, Jan, Carlos, Juan Date: December 10, 2013
Generic EtD framework 1
Evidence to decision framework
Question 1: Should probiotics vs. no probiotics be used in pregnant women?
Population:!pregnant!women!
Option:!probiotics!Comparison:!no!probiotics!Setting:3outpatient!Perspective:3individual!patient
Background: The$intestinal$microbiome$could$play$an$important$role$in$the$immune$system$maturation,$and$it$has$been$suggested$that$early6life$probiotic$administration,$whether$directly$to$the$infant$or$in$their$mothers$breast$milk,$may$reduce$the$risk$of$allergies$in$childhood.$The$objective$of$this$question$is$to$evaluate$the$impact$of$probiotics$administered$to$the$expecting$mothers$on$their$infant.
Subgroup considerations: subpopulation of women at high risk for allergy in a child
CRITERIA JUDGEMENTS RESEARCH EVIDENCE ADDITIONAL INFORMATION
PR
OB
LEM
Is the problem a priority?
No Probably no Uncertain Probably yes Yes
X
Allergic diseases represent a spectrum of health conditions and a worldwide burden in different populations. (1)
Are a large number of people affected?
No Probably no Uncertain Probably yes Yes
X
As many as 40% of the worldwide population is affected by any type of allergy. In infants prevalence depends highly on the allergic status of their parents, being approximately of 10% in those without an allergic parent or sibling, versus 20% to 30% in those with the atopic background in their relatives. (2)
Prepared by: Holger, Jan, Carlos, Juan Date: December 10, 2013
Explanations Prepared by: Holger, Jan, Carlos, Juan Date: December 10, 2013
Generic EtD framework 2
CRITERIA JUDGEMENTS RESEARCH EVIDENCE ADDITIONAL CONSIDERATIONS
VA
LUE
S
Is there important uncertainty or variability about how much people value the main outcomes?
Important uncertainty
or variability
Possibly important
uncertainty or
variability
Probably no
important uncertainty
or variability
No important
uncertainty or
variability
No known undesirable outcomes
X
Detailed judgements
The relative importance or values of the main outcomes of interest:
Outcome Relative importance Certainty of the evidence Eczema critical low
Asthma/wheezing critical low
Food allergy critical low
Adverse effects critical low
We judged that the outcomes eczema, asthma and food allergy are critical for people. The adverse outcomes are probably of high importance and the burden of taking daily pills is limited. Some immunocompromised women might not accept the risk.
BE
NE
FIT
S &
HA
RM
S O
F T
HE
OP
TIO
NS
What is the overall certainty of the evidence of effectiveness?
No included studies Very low Low Moderate High
X
Summary of findings:
Outcome With [intervention]
Without [intervention]
Difference (per 100) (95%CI)
Relative effect (RR)
(95%CI)
Certainty of the
evidence (GRADE)
Eczema (follow-up 1 to 5 years)
365/1520 (24%)
484/1515 (31.9%)
9 fewer per 100 (from 4 fewer to 13
fewer)
RR 0.72 (0.6 to 0.86)
⊕⊝⊝⊝ VERY LOW
Asthma/wheezing (follow-up 2 to 7 years)
143/992 (14.4%)
139/982 (14.2%)
0 fewer per 100 (from 3 fewer to 3
more)
RR 0.97 (0.77 to 1.22)
⊕⊕⊝⊝ LOW
Food allergy (follow-up 1 to 2 years)
36/279 (12.9%)
41/284 (14.4%)
1 more per 100 (from 3 fewer to 8
more)
RR 1.08 (0.73 to 1.59)
⊕⊝⊝⊝ VERY LOW
Adverse effects 101/394 (25.6%)
88/397 (22.2%)
3 more per 100 (from 4 fewer to 12
more)
RR 1.13 (0.82 to 1.52)
⊕⊝⊝⊝ VERY LOW
Link to detailed evidence profile Subgroup considerations: Link(s) to summary of findings and judgments for subgroups
The data are indirect for all outcomes because they are primarily derived from studies that looked at mixed exposure in women during pregnancy and breastfeeding and of infants after birth. Only 1 RCT assessed the effect on eczema in pregnant women only: RR 0.88 (0.63 to 1.22); RD 5 fewer per 100 (from 14 fewer to 9 more) 5 RCTs included pregnant women + later breastfeeding mothers: RR 0.5 (0.4 to 0.63); RD 21 fewer per 100 (from 15 fewer to 25 fewer) 5 RCTs included pregnant women + infants after birth (follow-up 1 to 5 years): RR 0.87 (0.72 to 1.04), RD 4 fewer per 100 (from 8 fewer to 1 more) 3 RCTs included pregnant women + subsequently breastfeeding + infants (follow-up 3 to 4 years): RR 0.78 (0.49 to 1.24); RD 7 fewer per 100 (from 17 fewer to 8 more) No effects were observed on asthma/wheezing and food allergy.
How substantial are the desirable anticipated effects?
Don’t know
Not important
Somewhat important
Moderately important
Very important
Varies
X
X
Detailed judgements
There was some disagreement among panel members whether the effect is somewhat or moderately important.
How substantial are the undesirable anticipated effects?
Don’t know
Very important
Moderately important
Somewhat important
Not important
Varies
X
Detailed judgements
No serious adverse effects, and no difference in mild adverse effects between the groups.
Do the desirable effects outweigh the undesirable effects?
No Probably No
Don’t know Probably Yes
Yes Varies
X
Detailed judgements
Prepared by: Holger, Jan, Carlos, Juan Date: December 10, 2013
Explanations Prepared by: Holger, Jan, Carlos, Juan Date: December 10, 2013
Generic EtD framework 2
CRITERIA JUDGEMENTS RESEARCH EVIDENCE ADDITIONAL CONSIDERATIONS
VA
LUE
S
Is there important uncertainty or variability about how much people value the main outcomes?
Important uncertainty
or variability
Possibly important
uncertainty or
variability
Probably no
important uncertainty
or variability
No important
uncertainty or
variability
No known undesirable outcomes
X
Detailed judgements
The relative importance or values of the main outcomes of interest:
Outcome Relative importance Certainty of the evidence Eczema critical low
Asthma/wheezing critical low
Food allergy critical low
Adverse effects critical low
We judged that the outcomes eczema, asthma and food allergy are critical for people. The adverse outcomes are probably of high importance and the burden of taking daily pills is limited. Some immunocompromised women might not accept the risk.
BE
NE
FIT
S &
HA
RM
S O
F T
HE
OP
TIO
NS
What is the overall certainty of the evidence of effectiveness?
No included studies Very low Low Moderate High
X
Summary of findings:
Outcome With [intervention]
Without [intervention]
Difference (per 100) (95%CI)
Relative effect (RR)
(95%CI)
Certainty of the
evidence (GRADE)
Eczema (follow-up 1 to 5 years)
365/1520 (24%)
484/1515 (31.9%)
9 fewer per 100 (from 4 fewer to 13
fewer)
RR 0.72 (0.6 to 0.86)
⊕⊝⊝⊝ VERY LOW
Asthma/wheezing (follow-up 2 to 7 years)
143/992 (14.4%)
139/982 (14.2%)
0 fewer per 100 (from 3 fewer to 3
more)
RR 0.97 (0.77 to 1.22)
⊕⊕⊝⊝ LOW
Food allergy (follow-up 1 to 2 years)
36/279 (12.9%)
41/284 (14.4%)
1 more per 100 (from 3 fewer to 8
more)
RR 1.08 (0.73 to 1.59)
⊕⊝⊝⊝ VERY LOW
Adverse effects 101/394 (25.6%)
88/397 (22.2%)
3 more per 100 (from 4 fewer to 12
more)
RR 1.13 (0.82 to 1.52)
⊕⊝⊝⊝ VERY LOW
Link to detailed evidence profile Subgroup considerations: Link(s) to summary of findings and judgments for subgroups
The data are indirect for all outcomes because they are primarily derived from studies that looked at mixed exposure in women during pregnancy and breastfeeding and of infants after birth. Only 1 RCT assessed the effect on eczema in pregnant women only: RR 0.88 (0.63 to 1.22); RD 5 fewer per 100 (from 14 fewer to 9 more) 5 RCTs included pregnant women + later breastfeeding mothers: RR 0.5 (0.4 to 0.63); RD 21 fewer per 100 (from 15 fewer to 25 fewer) 5 RCTs included pregnant women + infants after birth (follow-up 1 to 5 years): RR 0.87 (0.72 to 1.04), RD 4 fewer per 100 (from 8 fewer to 1 more) 3 RCTs included pregnant women + subsequently breastfeeding + infants (follow-up 3 to 4 years): RR 0.78 (0.49 to 1.24); RD 7 fewer per 100 (from 17 fewer to 8 more) No effects were observed on asthma/wheezing and food allergy.
How substantial are the desirable anticipated effects?
Don’t know
Not important
Somewhat important
Moderately important
Very important
Varies
X
X
Detailed judgements
There was some disagreement among panel members whether the effect is somewhat or moderately important.
How substantial are the undesirable anticipated effects?
Don’t know
Very important
Moderately important
Somewhat important
Not important
Varies
X
Detailed judgements
No serious adverse effects, and no difference in mild adverse effects between the groups.
Do the desirable effects outweigh the undesirable effects?
No Probably No
Don’t know Probably Yes
Yes Varies
X
Detailed judgements
Prepared by: Holger, Jan, Carlos, Juan Date: December 10, 2013
Explanations Prepared by: Holger, Jan, Carlos, Juan Date: December 10, 2013
Generic EtD framework 3
CRITERIA JUDGEMENTS RESEARCH EVIDENCE ADDITIONAL CONSIDERATIONS
RE
SO
UR
CE
US
E
How large are the resource requirements?
Large costs
Moderate costs
Small Moderate savings
Large savings
Varies
X
Detailed judgements
Prices are likely to vary substantially depending on the setting. This may be a particularly important consideration in low and middle-income countries. A level and type of insurance may play a substantial role as well. From a health systems point of view it might also be cost effective given that probiotic would be used for 9 months and cost of treatment of eczema may be distributed across many years.
Extremely limited research evidence (internet searches of drug prices)
Bifidobacterium bifidum (cost per person per year US$) Dose: 1 pill
each day
Lactobacillus gg (cost per person per
year US$) 1 pill each day
North-America
Average $181.16 $341.6
South-America
Average $174.3 $286
Europe
Average $167.86 $251.56
Fewer office visits would occur as a result of eczema if the effects on eczema were true.
How large is the incremental cost relative to the net benefit?
Very large ICER
Large ICER
Moderate ICER
Small ICER
Savings Varies
Detailed judgements
No research evidence
If eczema was reduced the intervention might be cost-effective given fewer office visits (between $17,400 and $34,100 to treat 100 people for 1 year or ¾ of that for 9 months) preventing 9 cases of eczema. In most studies probiotics were used in the last trimester of pregnancy, which, if used this same way, might reduce the cost per pregnant woman.
EQ
UIT
Y What would
be the impact on health inequities?
Increased Probably increased
Uncertain Probably reduced
Reduced Varies
X
Detailed judgements
No research evidence
In some settings it may be important to consider equity as the access may depend on socioeconomic status of the country or setting where coverage will depend on policymakers.
AC
CE
PT
AB
ILIT
Y
Is the option acceptable to key stakeholders?
No Probably No
Uncertain Probably Yes
Yes Varies
X
Detailed judgements
No research evidence
Prepared by: Holger, Jan, Carlos, Juan Date: December 10, 2013
Explanations Prepared by: Holger, Jan, Carlos, Juan Date: December 10, 2013
Generic EtD framework 4
CRITERIA JUDGEMENTS RESEARCH EVIDENCE ADDITIONAL CONSIDERATIONS
FE
AS
IBIL
ITY
Is the option feasible to implement?
No Probably No
Uncertain Probably Yes
Yes Varies
X
Detailed judgements
No research evidence
Prepared by: Holger, Jan, Carlos, Juan Date: December 10, 2013
Explanations Prepared by: Holger, Jan, Carlos, Juan Date: December 10, 2013
Generic EtD framework 5
Recommendation Should probiotics vs. no probiotics be used in pregnant women (exposing their children in utero)?
Overall balance of consequences Undesirable consequences clearly outweigh desirable
consequences
Undesirable consequences probably outweigh desirable
consequences
The balance of desirable and undesirable consequences indicates
they are very similar*
Desirable consequences probably outweigh undesirable
consequences
Desirable consequences
clearly outweigh undesirable
consequences
! ! ! X !
We recommend against the option or for the alternative
We suggest not to use the option or to use the alternative
We suggest using the option We recommend the option
! ! X !
Panel decisions 3 panel members with potential COI recused themselves from participating in formulating the recommendation. Consensus was obtained from the rest of the team.
Recommendation (text) The guideline panel suggests using probiotics in pregnant women at high risk for allergy in their children (conditional recommendation, very low quality evidence).
Remarks and justification Most studies commenced probiotics in the last trimester of pregnancy. The very low quality evidence for adverse effects indicates that our confidence in the absence of increased adverse effects is low. Future research is needed (see definitions of very low quality) e.g., generalizing to immune-compromised children
Subgroup considerations Women with high risk of allergy in their children Women with average risk of allergy in their children
Implementation considerations This recommendation is based on trials investigating the probiotics or mixtures of probiotic listed below. We have not found a difference between these different probiotics, but that does not mean there is no difference
Monitoring and evaluation considerations
Research priorities Develop instruments for evaluating the risk of allergy in children as the family history predicts only about 30% of the population risk. There is some evidence that first child is at higher risk for allergy than subsequent children. Long-term follow-up of long-term effects. No direct evidence for the use of probiotics in formula – this should be evaluated in future research and is an unmet need.
Prepared by: Holger, Jan, Carlos, Juan Date: December 10, 2013
OUTLINE
• what are clinical practice guidelines?
• why should we use them?
• what are recommendations and levels of
evidence?
• how to interpret a CPG recommendation?
tools / more readings
• guidelinedevelopment.org
• cebgrade.mcmaster.ca
• gradeing.cochrane.org
GRADEingMethods
Thank you! cuelloca@mcmaster.ca@CharlieNeck
�