Table 2.

Exploratory objectives and endpoints.

Exploratory objective	Exploratory endpoint
To assess the association of clinically relevant variations in QoL [EORTC QLQ-C30 and HN43 global scores (13, 14)] with disease recurrence and survival in HNC survivors within the study observation (up to 24 months) period during post-treatment follow-up.	Association of disease-free survival (DFS), event-free survival (EFS) and overall survival (OS) with clinically relevant variations (either increase or decrease, as appropriate according to scales) of EORTC QLQ-C30 and HN43 questionnaires, as defined in (13, 14).
To To analyze time-dependent variations of QoL (EORTC QLQ-C30 and HN43 scores) within the study observation (up to 24 months) period during post-treatment follow-up in HNC survivors assessing their association with recurrence and survival.	Association of disease-free survival (DFS), event-free survival (EFS) and overall survival (OS) with time-dependent clinically relevant variations (either increase or decrease, as appropriate according to scales) of EORTC QLQ-C30 and HN43 questionnaires, as defined in (13, 14).
To To analyze QoL scores (EORTC QLQ-C30 and HN43 scores) within the study observation (up to 24 months) period during post-treatment follow-up in nasopharyngeal cancer patients assessing their association with recurrence and survival.	Association of disease-free survival (DFS), event-free survival (EFS) and overall survival (OS) with clinically relevant variations (either increase or decrease, as appropriate according to scales) of EORTC QLQ-C30 and HN43 questionnaires, as defined in (13, 14), in nasopharyngeal carcinoma patients.
To reduce the proportion of HNC subjects experiencing a clinically meaningful deterioration in pre-specified EORTC QLQ-HN43 scales (not included in secondary endpoints) between at least 2 visits during post-treatment follow-up.	The proportion of HNC survivors experiencing a clinically meaningful deterioration [as defined in (13, 14)] of pre-specified EORTC QLQ-HN43 scales (pain in the mouth, problems with senses, body image, dry mouth and sticky saliva, coughing, social contact, neurological problems, sexuality, problems with shoulder, skin problems) within the study observation (up to 24 months) period during post-treatment follow-up.
For HNC survivors randomized in the BD4QoL platform group, using artificial intelligence techniques to build models to predict a QoL deterioration [EORTC QLQ-C30 and HN43 scores, EQ-5D-5L as defined in (7, 13, 14)] between at least 2 visits during within the study observation (up to 24 months) period during post-treatment follow-up.	The association of all the health-related data recorded by the BD4QoL platform Supplementary Material registered continuously within the study observation (up to 24 months) period during post-treatment follow-up with clinically relevant variations (either increase or decrease, as appropriate according to scales) of EORTC QLQ-C30 and HN43 questionnaires, as defined in (7, 13, 14)
To assess the association of clinically relevant variations of QoL [EORTC QLQ-C30 and HN43 global scores (13, 14)] with self-efficacy for coping with cancer in HNC survivors within the study observation (up to 24 months) period during post-treatment follow-up.	Association of clinically relevant variations (either increase or decrease, as appropriate according to scales) of EORTC QLQ-C30 and HN43 questionnaires, as defined in (13, 14), and self-efficacy for coping with cancer, defined as mean of the item scores at the CBI-B (11).
To reduce the proportion of HNC subjects experiencing a clinically meaningful deterioration of QoL between at least 2 visits during post-treatment follow-up, stratifying according to patients completing treatment within 12 months versus after 12 months.	The proportion of HNC survivors experiencing a clinically meaningful global health-related EORTC QLQ-C30 QoL deterioration [decrease ≥10 points, as defined in (13, 14)] within the study observation (up to 24 months) period during post-treatment follow-up. Stratification according to timing after study completion (less than 12 months versus more than 12 months)
To assess the economic impact on HNC survivor care and the viability, usability, and trust of using the BD4QoL platform (Health Technology Assessment, HTA).	Incremental Cost-Effectiveness Ratio measured in €/QALY. Measures of viability, usability, and trust.