Patient Preference for Risk Benefit Trade-Off of Disease Modifying Therapy Attributes

Background: Disease modifying therapies (DMTs) decrease relapses in patients with multiple sclerosis (MS). Due to their wide variety of risk/ benefit attributes, patients must weigh their preferences when choosing DMTs.

Objectives: We determine patient preferences for DMT’s risk/benefit attributes.

Methods: Our choice-based conjoint (CBC) survey developed using Sawtooth software was given in-person, to 300 consenting adults with relapsing remitting MS at University of California, San Francisco’s MS clinic. Each patient answered 16 choice tasks. They chose one of two choices with 3-4 different levels of 6 risk and benefit attributes of hypothetical DMTs.  Benefits included delayed progression, reduced relapses, and symptom improvement. Risks were mild side effects (SEs), serious SEs, and administration route and frequency.  Analysis used mixed-effects logistic regression.

Results: Patients were 76% female; 75% with mild, 18% moderate, and 7% severe disease.  All 6 attributes significantly impacted patient preference. Of the benefits, the preferences were highest for preventing progression 10 vs 2 years (odds ratio [OR]=2.27, p<0.001) and for substantial vs no improvement in symptoms (OR=3.67, p<0.001). Patients may be willing to accept a 0.05-0.1% risk of serious SEs leading to death (OR=0.57-0.66; p<0.001) to gain a moderate to substantial benefit from their therapy. A 1% risk of serious SE compared to no risk (OR=0.22, p<0.001) resulted in very low preference, but had a comparable magnitude in preference to a substantial improvement in symptoms vs no improvement (OR=1.60, p<0.001).  Compared to daily subcutaneous administration, patients preferred daily oral administration (OR=2.15, p<0.001), then monthly intravenous (OR=1.54, p<0.001), and then intramuscular weekly (OR=1.19, p<0.01).

Conclusions: Patients are willing to make risk/benefit tradeoffs in medication selection. Their strongest benefit preference is for treatments that improve their symptoms substantially (not a proven DMT benefit) and the least for relapse prevention (the primary outcome of many DMT clinical trials).  Oral and monthly administration is preferred.