## 2 Background and Related Work
### Quantifying Clinical Protocol Compliance  
In the medical domain, compliance metrics generally measure whether a clinical protocol was followed and to what degree. The measurement can take different perspectives, e.g., treatment compliance, patient adherence [31; 32] or provider adherence [17; 33] (see Figure 1). It can be measured through different methods, e.g., direct observation, self-reporting techniques, electronic monitoring, and documentation review [17]. Compliance assessment is mentioned typically in the context of _medical trials_. There, compliance is described as \"adherence to all the trial-related requirements, good clinical practice (GCP) requirements, and the applicable regulatory requirements. The investigator should not implement any deviation from, or changes in, the protocol without agreement by the sponsor and prior review and documented approval/favorable opinion from the IRB/IEC (institutional review board/independent ethics committee) of an amendment,  
Figure 1: Compliance in the medical domain defined, showing the general definition by the U.S. National Library of Medicine [34] and the different perspectives of patient adherence [31; 32] and provider adherence [17; 33], including the perspective of treatment compliance, as proposed in this paper. (Images by [PERSON]). except where necessary to eliminate an immediate hazard(s) to trial subjects or when the change(s) involves only logistical or administrative aspects of the trial (e.g., change in monitor(s), change of telephone number(s))\" [35]. Another context in which protocol compliance is often mentioned is _intervention studies_. The goal of such an intervention study is to evaluate whether using the clinical protocol indeed has the desired positive effect on patient health and safety. In various intervention studies, compliance was, however, measured in quite different ways. Here we present an overview of possibilities encountered in the literature. The protocol under consideration may define some aspects regarding the compliance measure. The first aspect concerns the _person_ performing the activities from the protocol. It can be healthcare providers [12; 36] or the patient or his/her family, e.g., that can evaluate the patients' compliance or adherence to the doctors' recommendations, for instance, regarding drug intake [37]. This aspect is also related to how we record the compliance. In the first case, the electronic health record (EHR) may be used to verify that certain activities were performed [38]. In the latter case, EHR information is not available, and the researchers must rely on observations [39] or human perception and judgment. In such a case, questionnaires or qualitative analysis techniques, such as focus group interviews, may be used to evaluate the compliance [40; 41]. In this paper, we focus on compliance by healthcare providers. Another important dimension resulting from the protocol is the _medical subject_ of the protocol. Does the protocol concern a continuous process [42] or does it define concrete action steps [43; 44]? In the first case, in [42], the authors analyze the case of continuous drug administration, namely vasopressors. The authors defined potential protocol deviations when a patient had pressure outside a predefined target range for more than four hours without adjustment of the vasopressor dose. Next, those deviations were divided into two groups as clinically-justified and non-clinically-justified. In addition to the number of deviation events, the number of days and number of patients with at least one deviation event were also reported, as well as their percentages. In the latter case [43; 44], the protocol defines concrete action steps or activities. Hence, the next logical question is how to measure compliance with those steps. Two possibilities were given in [45] by measuring whether an activity was completed within a certain, prescribed time frame or was not executed at all. Another solution was used in [36].