1. IVIG guideline update Signal Detection Analysis
Alan Tinmouth
April 25, 2016

2. Ottawa EPC Project Team: Nadhera Ahmadza
Objective
To assess the currency of the following two clinical practice guideline recommendations using the Ottawa EPC’s method for qualitative signal detection approach: 
Guideline on the use of Intravenous Immune Globulin (IVIG) for the following 22 Neurologic conditions.
Guideline on the use of Intravenous Immune Globulin (IVIG) for the following 18 Hematologic conditions.
Ottawa EPC Project Team: Nadhera Ahmadza
Roxanne Ward
Becky Skidmore
Chantelle Garritty
Brian Hutton

3. Signal detection process

4. Signal detection process

5. IVIG Signal Detection Progress to date
Phase I:
Locating disease specific recommendations (for or against) in the original guideline (IVIG use for hematologic 18 conditions; IVIG use for neurologic 22 conditions).
 Completed (Expert opinion matrices)
Developing a matrix to be sent to experts that will list the guideline recommendations.
Contacting experts and seeking their opinion on whether new evidence suggests any of the followings for the intervention(s) of interest in the population stated in the specific recommendation
 Completed (Expert opinion matrices)
☐ Additional experts contacted for HDN, FNAIT, Epilepsy, ADEP

6. IVIG Signal Detection Progress to date
Phase I – Review of expert opinions, and targeted search by disease
CIDP
Expert Review
2/6 – guideline’s recommendations no longer valid
4/6 – aware of new evidence invalidating recommendations
Evidence Review
Evidence of long term therapy maintenance with IVIG up to 48 weeks
Improved outcomes compared with methylprednisilone
Conclusion
Signal detected.

7. IVIG Signal Detection Progress to date
Phase I – Review of expert opinions and targeted search by disease
Multifocal Motor Neuropathy
Expert Review
1/5 – guideline’s recommendations no longer valid
3/5 – aware of new evidence invalidating recommendations
Evidence Review
Cross-over study and observational transition showing equal effectiveness of IVIG and SCIG
RCT demonstrating improved outcomes with IVIG vs. placebo
Observational study reported improved outcomes with higher dose in non-responsive patients
Conclusion
Signal identified

8. IVIG Signal Detection Progress to date
Phase I – Review of expert opinions and targeted search by disease
Polymyositis
Expert Review
3/6 – did not know if guideline’s recommendations still valid
1/6 – aware of new evidence invalidating recommendations
Evidence Review
2 studies of IVIG in dematomyositis and polymyositis did not differentiate between conditions.
One RCT showed no difference compared to placebo
One observational study showed improvement post IVIG
Conclusion
No signal identified.

9. IVIG Signal Detection Progress to date
Phase I – Review of expert opinions and targeted search by disease
Dermatomyositis
Expert Review
1/6 – guideline’s recommendations no longer valid
2/6 – aware of new evidence invalidating recommendations
Evidence Review
2 studies of IVIG in dematomyosiitis and polymyositis did not differentiate between conditions.
One RCT showed no difference compared to placebo
One observational study showed improvement post IVIG
Conclusion
No signal identified.

10. IVIG Signal Detection Progress to date
Phase I – Review of expert opinions and targeted search by disease
Diabetic neuropathy
Expert Review
2/6 – did not know if guideline recommendations still valid
1/6 – aware of new evidence invalidating recommendations
Evidence Review
No evaluable studies
One suggested study had no comparator
Conclusion
No signal identified.

11. IVIG Signal Detection Progress to date
Phase II – Provisional literature search
Conducting an updated electronic search
Single search for all neurologic and hematologic conditions
Top 7 medical journals
Top 166 specialty journals
68 hematology journals and 98 neurology journals
5064 records after de-duplication
Screening the retrieved records
Currently underway

12. IVIG Signal Detection Work to come
Phase I - Review of expert opinions and targeted searches
Review of expert opinions completed (except 4 conditions)
For most conditions, previous guidelines still applied or experts did not know if guidelines still valid
Targeted searches ongoing
Final reports on 2 to 4 conditions per month
Completion Fall 2016
Phase II – Provisional literature search
Review of records starting