## 3 Results
### PRO as a Research and Drug Testing Tool  
Historically, PRO is a product of different healthcare developments. Thus, the collection of patient data is traced all the way back to the Crimean War (1854), where [PERSON] initiated a systematic collection of data regarding soldiers' cause of death [23; 24]. Furthermore, PRO is connected to certain disease-specific and generic health measures, developed since the 1940s [25; 26]. Measures initially perceived as indicators of \"outcomes\" and \"health status\"; however, as the collection and development of health status assessment measures evolved during the 1970's the concept of \"quality-of-life\" (QoL) gained ground; subsequently, paving the way for \"health-related quality-of-life\" (HRQoL) measures [26; 27; 28]. The same period, where theoretical frameworks such as e.g., [PERSON]'s structure-process-outcome model (1966) [29] and the biopsychosocial model (1977) emerged [30]. Furthermore, the 1970s was the decade where the collection of aggregated PROs was initiated in Sweden, establishing the beginning of systematic integration of PROs into national clinical databases [31; 32]. Later on, [PERSON]'s (1988) ideas regarding the separation of health status and psychosocial outcomes in chronic disease care were introduced, marking a shift regarding the relevance of patient participation and patient empowerment, essentially, accentuating a less paternalistic healthcare approach [33]. During the last part of the 20 th century, the evidence-based medicine approach gained support, emphasizing systematization, measurability and standardization of healthcare interventions [23; 34], paradigmatic aspects, aligned with focal methodological requirements concerning PRO instruments [11].  
Originally, PRO was used for group-level research and medical research [26; 35], as secondary endpoints in clinical trials [36; 37], e.g., when testing new drugs [38; 39] or evaluating the comparative effectiveness of healthcare interventions [40; 41]. Hence, the collection of PRO data established a systematic approach eliciting patients' perspectives on how healthcare interventions affected their health status [35]; whether they, for example, experienced adverse effects [27; 28], side-effects [38], comorbidity or an increased burden of illness due to a specific treatment [26]. PRO data is also useful in cases where treatments or drugs have almost similar clinical efficacy [42] since it might help explain non-compliance with the drug regime based on patients' experiences [32], potentially enhancing appraisals of drugs effect [11; 30]. Consequently, the FDA made the use of PROs to support claims in approved medical product labelling mandatory in 2009 [11].  
Thus, considering PROs genealogy and original application the International Society for Quality of Life Research (ISOQOL) definition of PRO as: \"... a measurement of any aspect of a patient's health that comes directly from the patient, without interpretation of the patient's response by a physician or anyone else\" [43], is quite fitting. An interpretation having commonalities with the FDA version elaborated upon in the introduction; however, ISOQOL explicitly refers to PRO as a measurement tool.