Table 1.

Study objectives and endpoints.

Objective			Endpoint
Primary
	To evaluate participant engagement with PEAR-008 compared to that with reSET-O. The hypothesis is that PEAR-008 group will have significantly greater participant engagement than the reSET-O group.	Number of active sessions with PEAR-008 or reSET-O per week
Secondary
	To evaluate the impact of PEAR-008 compared to reSET-O on treatment retention	Time to dropout (last contact with a participant)
	To evaluate the impact of PEAR-008 compared to reSET-O on abstinence from illicit opioids	Abstinence will be defined as abstinence on patient self-reports (via timeline followback) and the absence of nonbuprenorphine opioids on saliva drug screens. Abstinence (binary outcome: yes or no) will be determined 9 times, weekly during weeks 1-8 and at week 12.
	To evaluate participants’ digital therapeutic use patterns of PEAR-008 compared to reSET-O	Session duration; number of lessons and chapters completed; number of completed self-report assessments; response to notifications
	To evaluate the impact of PEAR-008 compared to reSET-O on change in psychiatric symptom severity between baseline and follow-up	Depression symptoms with Patient Health Questionnaire–8; Anxiety symptoms with Generalized Anxiety Disorder–7
	To evaluate the impact of PEAR-008 compared to reSET-O on change in recovery capital and resilience between baseline and follow-up	Brief Assessment of Recovery Capital–10; Connor-Davidson Resilience Scale–10
	To evaluate participant motivation and satisfaction over time with PEAR-008 compared to reSET-O	Participant surveys administered at baseline, week 4, week 8, and week 12; participant interview at follow-up
	To evaluate a more global measure of engagement by combining data from secondary endpoints 3-6	A multivariate analysis of variance combining data from secondary endpoints 3-6
Exploratory
	To evaluate the association between engagement with PEAR-008 compared to reSET-O and treatment outcomes (abstinence and retention)	Daily and weekly use patterns; saliva (or urine drug screen for AREFa participants only) and self-report; time to dropout
	To evaluate skills acquisition at week 4 and week 8 of PEAR-008 compared to reSET-O	Cognitive Behavioral Therapy Skills Questionnaire
	To evaluate medication adherence of PEAR-008 compared to reSET-O	Saliva drug screen (or urine drug screen, for AREF participants only)

^aAREF: Addiction Research and Education Foundation.