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

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

Signal detection process

Signal detection process

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

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I – Review of expert opinions, and targeted search by disease CIDP Expert Review 2/6 – guideline’s recommendations no longer valid 4/6 – aware of new evidence invalidating recommendations Evidence Review Evidence of long term therapy maintenance with IVIG up to 48 weeks Improved outcomes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

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opinions and targeted search by disease Multifocal Motor Neuropathy Expert Review 1/5 – guideline’s recommendations no longer valid 3/5 – aware of new evidence invalidating recommendations Evidence Review Cross-over study and observational transition showing equal effectiveness of IVIG and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

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.

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.

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.

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

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