Development and Evaluation of a Patient-Reported Outcome ( PRO ) Scale for Breast Cancer

Patient-reported outcomes (PROs) comprise a recently proposed evaluation system of therapeutic efficacy that is based on the subjective feelings of patients. A PRO directly reflects patients’ perspectives on various aspects of their health statuses Data obtained by PRO measurements provide evidence for therapeutic efficacy from the perspectives of patient. PRO includes the functional status or objective symptom indices and health-related quality of life. PRO also includes a patient’s satisfaction towards treatment. PRO equally emphasizes the quality-of-life index, the objective symptom index and the non-entity index. Using this knowledge as a guide and modern mathematical statistics as a tool, this study preliminarily established a PRO scale for evaluating breast cancer after


Introduction
Patient-reported outcomes (PROs) comprise a recently proposed evaluation system of therapeutic efficacy that is based on the subjective feelings of patients. A PRO directly reflects patients' perspectives on various aspects of their health statuses Data obtained by PRO measurements provide evidence for therapeutic efficacy from the perspectives of patient. PRO includes the functional status or objective symptom indices and health-related quality of life. PRO also includes a patient's satisfaction towards treatment. PRO equally emphasizes the quality-of-life index, the objective symptom index and the non-entity index. Using this knowledge as a guide and modern mathematical statistics as a tool, this study preliminarily established a PRO scale for evaluating breast cancer after surgery (Zhao et al., 2005;Cella et al., 2007;FDA., 2007;Pusic et al., 2009;Arbuckle et al., 2010; The molecular typing-based, individualized precision therapy for breast cancer warrants a good survival rate for breast cancer. A large number of breast cancer patients achieve postoperative long-term survival or manage to survive in the presence of tumours. However, the vast majority of patients experience a variety of health, psychological and behavioural problems related to the disease. Patients suffer not only the general psychological burden of malignant tumours but also the immense psychological impact caused by loss of a breast. The inclusion of PROs in the evaluation of clinical treatment not only compensates for the current lack of indices for evaluating the clinical efficacy of breast cancer treatment but also allows a patient's condition to be assessed more accurately than would be possible with universally applicable scales without PROs. (Pusic et al., 2009;Kanatas et al., 2012;Ohsum et al., 2013; Internationally, the quality-of-life scales that are extensively employed for breast cancer have served an important role in guiding our research. This study represents a bold attempt and innovation. Application of the PRO scale in the evaluation of the clinical efficacy of individualized breast cancer therapy is the direction of our research.

Generation of primary questionnaire and implementation of clinical survey
Using the established method of formulating PRO scale as reference, a group composed of breast cancer patients, medical experts and statistical experts was set up, and an envisioned conceptual structural model of a breast cancer-specific PRO scale was established. The model had a five-dimensional structure that consisted of five domains, including physiology, psychology, independence, social relations and the environment.

Selection of items of the PRO scale
The methods that were employed to coarsely screen the items included item difficulty analysis and response analysis. The items were re-screened using the following methods: Dispersion tendency analysis and stepwise regression analysis. In the pre-survey, the total score given by patients to their quality of life represents the total situation of the quality of life of patients. Factor analysis and cluster analysis were used to select items based on representativeness. Discriminant analysisthis method primarily selects items from the aspect of distinguishability. Cronbach's coefficient-this method primarily selects items from the aspect of internal consistency. In this study, the items were classified and examined based on the theoretical structure that was used to design the scale.

Scientific assessment of the PRO scale
A scientific assessment of the feasibility, reliability and validity of the PRO scale was conducted. The scientific assessment was completed using the SPSS 15 statistical software package. During the assessment of the structural validity of the scale, the confirmatory factor analysis, the affiliate software of SPSS 15.0-AMOS 7-was employed. The feasibility assessment included the clinical usage of the breast cancer-specific PRO scale and the time required to complete the scale. The reliability assessment adopted two common methods: Cronbach's α coefficient and split-half reliability. The validity of the PRO scale was primarily evaluated from three aspects: content, structure and distinguishability. Assessments of construct validity included an exploratory factor analysis and a confirmatory factor analysis (Anthoine et al., 2014;Fiscella et al., 2011;Luquiens et al., 2015;Mills et al., 2010;McAllister et al., 2011).

Generation of the preliminary version of the PRO questionnaire
Patients who satisfied the diagnostic criteria for breast cancer, already underwent surgery, were capable of expressing their opinions and had no mental illness were included. The patients were interviewed from different aspects and appropriately guided. The information was collected and summarized into items. A clinical survey was conducted using the preliminary questionnaire in the breast surgery clinics of three major hospitals. A total of 200 patients were interviewed. A total of 67 questionnaire items was generated; this number was revised by breast surgery experts. After these revisions, 55 items were included in the preliminary version of the  PRO questionnaire (Table 1). These items of the proposed scale were divided into the following five domains: physiology, psychology, personal life, social relations and social environment.

General information about the samples
A total of 479 female outpatients were examined. The majority of patients (51.6%) ranged between 35 and 50 years of age. The distribution of the course of disease  Table 2).

Results of various screening methods and the final structure of the breast cancer-specific PRO scale
In the process of reviewing and screening the items, the items selected by different methods were not completely identical. Therefore, a combination of various methods was employed, and the items that were selected by all methods or more than half of the methods were employed in the questionnaire. Some items cannot be determined by these methods. In these cases, the screening methods were combined with certain features of the item, such as professional knowledge and operability, and scale reliability and validity assessment to determine whether the item should be included or excluded. A total of four domains and 37 items were reserved. In addition, a self-evaluation item regarding the quality of life was added. Therefore, a total of 38 items were included in the questionnaire (Tables 3 and 4). The structure of the final version of the breast cancer-specific PRO scale is presented below (Table 5).
Based on the structure, the score of a domain/aspect of the scale was the cumulative score of the items that belonged to the domain/aspect. A grading system was set up to classify the items in the PRO scale into five grades. The five grades had scores of one, two, three, four or five points, where one point denoted the worst grade and five points denoted the best grade. High scores indicate a high quality of life, whereas low scores indicate a low quality of life. However, various domains contained different numbers of items, which hindered the comparison between the scores of the domains. Therefore, the average score of each domain was calculated, which enabled a comparison between the domains.   The results of the reliability assessment showed that the breast cancer-specific PRO scale exhibited good reliability. The results also indicated that the related syndrome elements only experienced a low degree of disturbance in the process of utilizing the scales to summarize the pathogenesis of breast cancer, which may clarify the main symptom of the clinical syndrom. The validity results showed that the first factor included items that reflected information in four domains: psychology, independence, social relationships and social environment. Therefore, we believe that the PRO scale possessed not only construct validity but also content validity. Therefore, the study findings indicated that the current PRO scale exhibited satisfactory discriminant validity .

Discussion
PRO measures not only evaluate the efficacy of a stage of treatment but also serve a certain guiding role in the next stage of treatment. Based on the screening results, the items that we proposed to address complications were reserved; this finding was consistent with clinical situations. Regarding the side effects of radiochemotherapy and endocrine therapy, items including gastrointestinal reactions and hair loss were removed based on the screening results. The medical cases selected for this study involved patients who received surgery more than six months ago, these symptoms have minimal effects on the total health of the patients. Items reserved in the final version of the PRO scale addressed the side effects, including the side effects of endocrine therapy, drug-induced osteoporosis, and toxic reactions of the cardiovascular system induced by Adriamycin and other chemotherapy drugs. These side effects are long-lasting and have a significant impact on the health of the patients.
The results showed that the majority of the deleted items were derived from FACT-B. Most patients gave more attention to subjective feelings of symptoms instead of the quality of life when completing the questionnaire. According to the patients, the discomfort symptoms caused additional suffering. The results are consistent with our expectations. A PRO emphasizes subjective feelings. The focus of PRO differs from the focus of the quality of life scales and readily reflects the significance of developing PROs. The items in the PRO scale that belong to the domains of social relations and environment were also screened. The results showed that the items that address marriage, sexual life and emotions should be deleted. We believe that many patients do not provide accurate real answers due to pride or other reasons. Therefore, we should protect patients' rights of privacy in future studies. Therefore, the scale failed to successfully evaluate the long-term therapeutic efficacy. In addition, the scale was unable to reflect dynamic changes over time.
We will continue to enrich the content and improve the construction of the PRO scale to obtain better evaluations of therapeutic efficacy.