Introduction
Shoulder pain is one of the most prevalent musculoskeletal disorders, after low-back and knee pain, with a global prevalence of 16–26%1,2). The condition originates not only from the shoulder-girdle joint, represented by the glenohumeral (GH) joint, but also from the surrounding soft tissues of the scapular and upper arm regions3). Patients commonly experience functional impairments that limit work performance, daily activities, and sports participation, leading to psychological distress and a reduced quality of life4). Shoulder pain also imposes a significant economic burden worldwide5,6). In Korea, the total number of patients with shoulder disorders rose from 35,798 patients in 2010 to 42,558 in 2019, while related healthcare costs also showed an upward trend, rising from USD 5,485,196 to USD 11,522,543, respectively7).
The growing prevalence and associated physical and economic impact of shoulder disorders have increased the demand for effective treatment options. Consequently, patients have adopted several Traditional Korean medicine (TKM) modalities, including acupuncture (AT), moxibustion, cupping, and warm- or cold-therapy7). Among these, AT is the most widely used and has demonstrated substantial effectiveness in alleviating shoulder pain7,8). However, its efficacy in improving functional limitations such as limited range of motion (ROM) remains controversial8). Therefore, exercise-based therapies that enhance shoulder joint function and range of motion (ROM) have attracted attention from patients with shoulder pain seeking to improve their satisfaction and achieve optimal therapeutic outcomes9,10).
Daoyin Exercise Therapy (DET) is derived from the traditional Daoyin method, combining therapist -guided passive muscle and joint movements (bending, stretching, and tapping) with controlled breathing to relieve pain and restore neuromuscular function11,12). DET is distinguished from conventional exercise therapy and Chuna manual therapy by the nature of therapist–patient interaction. Conventional exercise therapies primarily rely on the patient’s active movement, with limited therapist involvement through instruction, supervision, or correction. Chuna manual therapy mainly consists of practitioner-delivered manipulative techniques involving externally applied forces, during which the patient remains passive or participates minimally through resistive input, such as in joint mobilization or muscle energy techniques11). In contrast, DET integrates the patient’s active movement with the therapist’s active guidance through direct facilitation of motion, promoting functional recovery and highlighting its bidirectional and interactive therapeutic nature11). Furthermore, DET incorporates personalized breathing techniques grounded in a holistic rehabilitation approach, which help reduce muscle tightness, promote structural stabilization, induce mental relaxation, and enhance systemic metabolism as part of a mind–body holistic approach13–15). In addition, its gentle movements are well suited for older adults, providing physical strength improvement without imposing excessive physical burden16).
Given these characteristics, DET appears promising for managing shoulder disorders9,10). In Korean clinical practice, DET is commonly used as an adjunct therapy to AT for pain management17,18). Regarding shoulder pain, a case report demonstrated its effectiveness in treating supraspinatus tendon tears, and a systematic review highlighted its potential in reducing the shoulder pain15,19). The clinical significance of shoulder pain management lies in identifying and optimizing effective DET techniques, which will serve as the foundation for a standardized clinical protocol. However, there is a lack of pragmatic trials applying DET as an adjunct to TKM therapies, particularly in terms of functional outcomes and cost-effectiveness compared to conventional TKM therapies.
Taking these into account, it is necessary to evaluate both the therapeutic and economic benefits of DET as an adjunct therapy for shoulder pain. Therefore, this study aims to assess the efficacy, safety, and cost-effectiveness of DET in combination with AT for shoulder pain through a rigorously designed, multicenter, pragmatic randomized controlled trial (RCT).
Method
1. Study Design
This is a multicenter, open-label, single-blinded (assessor-blinded), pragmatic, randomized clinical trial with two parallel arms. The intervention group will receive DET in combination with AT, while the control group will receive AT alone. The trial is registered in the Clinical Research Information System (CRIS), Korea (KCT009085). Three Korean research centers will conduct the trial between December 21, 2023 and December 31, 2024: Dongguk University Bundang Oriental Hospital (Seongnam), Kyunghee University Oriental Medicine Center (Seoul), and Daejeon Korean Medicine Hospital at Daejeon University (Daejeon). Participants will undergo screening at their initial visit, and those deemed eligible will receive 12 treatment sessions over 6 weeks (two sessions per week). Follow-up will occur by telephone one month after the final visit (Figure 1).
2. Participants and Eligibility Criteria
Outpatients with unilateral shoulder pain who meet the eligibility criteria will be recruited from the Department of Korean Rehabilitation Medicine at each of the three aforementioned hospitals. Those who want to participate will receive a brief explanation of the study, including potential benefits and risks. After obtaining written informed consent from each participant, demographic data will be collected, a physical examination will be conducted, and a medical history assessment will be performed.
The specific eligibility criteria are stated:
Inclusion criteria
Aged between 19 to 65 years
Unilateral shoulder pain lasting at least 6 weeks but less than 12 months, accompanied by functional impairment.
Moderate to severe pain intensity and functional impairment, considering the Numerical Rating Scale (NRS) ≥ 4, and the Shoulder Pain and Disability Index (SPADI) ≥ 40
No communication difficulties
Voluntarily signed written informed consent
Exclusion
Shoulder pain originating from conditions other than the shoulder: lung, heart, cervical spine, stroke, spinal cord injury, or surgery
History of shoulder surgery
Diagnosed with a shoulder fracture or dislocation
Deemed inappropriate for DET: dermatitis at the contact point for DET, and surgical history of other regions that may affect shoulder motion
Implemented other pain-related interventions that may interfere with the study outcomes: Taking non-steroidal anti-inflammatory drugs within the last two weeks, receiving steroid injections within the last month
Pregnancy
Possibility of full-thickness rotator-cuff tear or inflammatory arthritis based on physical examination
Participation in another clinical trial within the last three months
Any other disqualifying condition identified by the investigator
3. Randomization and Allocation Concealment
Participants who meet the eligibility criteria and voluntarily provide written informed consent will be randomized. To ensure equal allocation to the intervention and control groups, randomization will be performed in a 1:1 ratio by a computer-generated random-digit table with variable block sizes of 4, 6, and 8. The allocation results will be sealed in opaque envelopes and stored in a double-lock cabinet by a third party not involved in the trial. The designated researcher at each research center will open the envelope in the participant’s presence at the second visit. After allocation, the assignment cannot be changed and will remain confidential to other researchers until all assessments and statistical analysis are complete.
4. Blinding
Blinding of patients and practitioners will not be feasible in this trial, as only the group receiving DET will have close contact between the practitioner and patient for exercise sessions. Accordingly, the study will be single-blinded: outcome assessors and statisticians will remain unaware of group assignments, while personnel involved in allocation or treatment will not take part in outcome assessment or data analysis. To further minimize potential detection bias in patient-reported outcomes (SPADI, NRS, EQ-5D-5L, and EQ-VAS), all questionnaires will be administered, distributed, and collected by a blinded research assistant using a standardized instruction script. Participants will complete the questionnaires independently, without any discussion with clinicians or assessors, to ensure uniform administration conditions.
5. Interventions
1) Daoyin Treatment
DET will be applied only to the intervention group after AT, under aseptic conditions. Practitioners will disinfect their hands prior to the procedure to ensure infection control. The intervention group will receive DET twice a week for 6 weeks, totaling 12 sessions. Treatment will be performed by TKM physicians certified by the Korean Ministry of Health and Welfare who have completed at least six years of formal education at TKM college and possess a minimum of one year of clinical experience.
The DET technique applied in this study will be standardized across the three centers through a pre-trial training session and the distribution of the DET protocol. The protocol was developed by a research team in collaboration with the Clinical Practice Guideline Development Committee experts for Shoulder Pain and five advisors from relevant professional and academic societies. The final protocol was determined following a comprehensive review of two academic societies.
The DET techniques in the protocol include exercises with personalized breathing aimed at modulating the function of the rotator-cuff and surrounding muscles, thereby stabilizing the shoulder joints. DET will relieve muscle tightness and facilitate movement in a realigned position, improving joint contracture, restricted mobility, and malalignment. Given that this is a pragmatic trial, DET techniques will be selected from the protocol based on their appropriateness for each patient’s functional impairments.
Specifically, active assistive exercises combined with breathing will initially be applied to muscles with functional limitations, followed by passive assistive exercises for joints with contractures or movement restrictions. An evaluation of the shoulder girdle muscles will be conducted to assess muscle tightness and movement limitations. The shoulder girdle muscles include the supraspinatus, infraspinatus, teres minor, subscapularis, teres major, deltoid, pectoralis major, latissimus dorsi, rhomboid, biceps brachii, and triceps brachii. Active assistive exercises will be applied to the muscles identified as abnormal during the assessment.
Subsequently, DET will be applied to the shoulder girdle joints, including the acromioclavicular (AC) joint, scapulothoracic joint, and glenohumeral (GH) joint. Prior to the application of DET, the scapular position will be assessed based on the anatomical landmarks of the superior angle, scapular spine, medial border, inferior angle, and the AC joint. Throughout this comprehensive assessment, the scapular alignment will be determined in terms of abduction/adduction, internal/external rotation, and elevation/depression. Based on the results of these evaluations, a subset of the five techniques will be selectively applied: 1) AC joint technique for cases with distal clavicular elevation; 2) the Scapula technique for depressed, retracted and downward rotated scapulae; 3) GH joint type 1 technique for elevated and protracted scapulae; 4) GH joint type 2 technique for patients with thoracic kyphosis; and 5) Scapula with GH joint technique for scapula instability. Each session will comprise three sets, with six repetitions per set. At the end of each set, the joint will be held at its maximum range for 3 seconds to ensure sufficient proprioceptive stimulation (Table 1).
2) Acupuncture Treatment
The enrolled participants will receive AT regardless of their assigned group. AT will be performed by TKM physicians who hold the same qualifications as those administering DET. Both groups will receive the same duration and frequency of sessions: two sessions per week, conducted over a 6-week period, including 12 sessions. AT will be performed after the skin surface is disinfected, with participants positioned in a lateral decubitus position with the affected side facing upward. Sterile AT needles, measuring 0.30 x 40 mm, will primarily be used for treatment. However, the needle size may be adjusted at the practitioner’s discretion to sizes such as 0.20 x 30 mm, 0.25 x 30 mm, and 0.25 x 40 mm. The primary acupoints will include GB21 (Gyeonjeong), LI14 (Bino), LI15 (Gyeonu), LI16 (Geogol), LU1 (Jungbu), SI9 (Gyeonjeong), SI11 (Cheonjong), SI14 (Gyeonoesu), and TE14 (Gyeollyo). Considering that this is a pragmatic trial, practitioners may adjust the acupoint selection as needed; however, distal acupoints are not permitted. AT will be applied for 15 minutes, with needle depths ranging from 5 to 20 mm intramuscularly to ensure the sensation of Deqi.
3) Usual care
For the control group, no additional education, advice, or self-exercise instruction for shoulder pain will be provided, as AT alone is considered an effective strategy for pain management. This approach is also intended to preserve the internal validity of group comparisons and to prevent potential contamination of treatment effects.
6. Outcome Measurement
1) Primary Outcome
The Shoulder Pain and Disability Index (SPADI) will be used as the primary outcome measure to evaluate the effectiveness of DET at 2nd visit(baseline), at the 7th visit, and at the 13th visit (endpoint), as well as at follow-up. SPADI is one of the most commonly used indices, consisting of two subscales to measure pain and functional disabilities of the shoulder. The pain subscale comprises five questions, with a total score of 50, while the disability scale includes 8 questions with a total score of 80. Higher scores indicate more severe shoulder impairments.
2) Secondary Outcomes
The Numerical Rating Scale (NRS), Active Range of Motion (AROM) of the shoulder, EuroQol-5 Dimensions-5 Level (EQ-5D-5L), and EuroQol visual analogue scale (EQ-VAS) will be used as secondary outcome measures. The measures will be assessed:
The NRS is a pain intensity scale ranging from 0 to 10, which will be measured at every visit and at follow-up to evaluate the level of pain experienced over the past week.
AROM of flexion, extension, abduction, adduction, external rotation, and internal rotation will be measured at each visit and follow-up. A nominated evaluator will assess AROM using a protractor according to a standardized protocol distributed to the three centers.
Health-related quality of life will be assessed using the EQ-5D-5L, a generic instrument that measures quality of life across five dimensions: self-care, usual activities, pain or discomfort, anxiety or depression, and social isolation. Each dimension is assessed on a scale of five levels of severity, ranging from 1 (no problem) to 5 (extreme problem). In addition, the patient’s current health status is assessed using the EQ-VAS, which ranges from 0 to 100 (0 = worst health condition imaginable to 100 = best health condition imaginable)20). Assessment will be conducted at 2nd (baseline), 7th, 9th, and 13th (endpoint) visits, as well as at follow-up (Table 2).
3) Adverse Events
All adverse events (AE), regardless of their relationship to DET, will be documented at every visit. The symptoms and signs of the AE, actions taken for AE, onset (if known), severity, course (i.e., continuous or intermittent), outcome, and causal relationship to the treatment will be recorded in the case-report form. The causal relationship between the AE and each treatment will be assessed using the 6-step scale of the World Health Organization-Uppsala Monitoring Center (WHO-UMC) system21). The severity of the AE will be evaluated using Spilker’s three-step classification method, which categorizes AE as mild, moderate, or severe22). Additionally, the patient’s vital signs will be assessed at every visit prior to treatment, and laboratory tests for the following items will be performed at the 1st (screening) and 13th (endpoint) visits: WBC, ESR, CRP, RBC, Hb, Hct, and fasting glucose.
7. Sample Size Estimation
The sample size was estimated using STATA 16 (StataCorp, College Station, TX, USA). As sample size estimation commonly refers to data from previous trials with a similar design, we reviewed existing RCTs. Most studies applied exercise therapy as the control8,10,23). Only J. Salom-Moreno et al. (2017) adopted AT as a comparator and, therefore, considered it the most appropriate reference for our trial24). We use their standard deviation for estimation. However, J. Salom-Moreno et al. (2017) reported no differences between the groups due to the short-term assessment of treatment effects within 72 hours24). Therefore, the Minimum Clinically Important Difference (MCID) for SPADI was considered for sample size calculation25). Based on these considerations, the two-sided significance level (α) was set at 5%, and the statistical power (1–β) at 80%. Reflecting the MCID of SPADI, an effect size of 8 points and a standard deviation of 12 were assumed. As a result, the required sample size was determined to be at least 37 participants per group. Considering an expected drop-out rate of 10%, 82 participants (41 patients per group, assuming a 1:1 allocation ratio) will be recruited for the study. The allocation of participants across each research center will be as follows: 30 participants at Dongguk University Bundang Oriental Hospital, 20 at Kyunghee University Oriental Medicine Center, and 32 at Daejeon Korean Medicine Hospital, affiliated with Daejeon University.
8. Data Analysis
This trial aims to evaluate the therapeutic effect, safety, and cost-effectiveness of DET as an adjunctive therapy to acupuncture for shoulder pain. To compare outcomes with the AT control group, data will be analyzed using both intention-to-treat (ITT) and per-protocol (PP) methods, with a 95% confidence interval, in IBM SPSS Statistics version 21 for Windows (IBM Corp). The ITT analysis will serve as the primary analysis, and PP analyses will include only participants who received eight or more treatment sessions.
Missing data of effectiveness outcomes (SPADI, NRS, AROM, and EQ-5D-5L) will be primarily handled using the last observation carried forward (LOCF) method, and multiple imputation will be applied if needed. On the other hand, missing data for safety outcomes (AEs and laboratory tests) will not be imputed and will be treated as missing. The accepted level of significance for all analyses will be p< 0.05. Data analysis will be conducted by statisticians independently from patient allocation and treatment.
Between-group comparisons of demographic characteristics will be performed using independent two-sample t-tests or Wilcoxon rank-sum tests for continuous variables, and chi-square or Fisher’s exact tests for categorical variables, as appropriate, based on the results of the Shapiro–Wilk test.
For effectiveness outcomes, a mixed ANOVA will be conducted to examine the group, time, and group-time interaction effects, with estimated marginal means computed for interpretation. Post-hoc pairwise comparisons at each time point will be performed using the Bonferroni correction. If significant group differences or potential confounders are identified in demographic characteristics, an ANCOVA will be performed including these variables as covariates. If the assumptions of normality or homogeneity of variance for ANOVA are severely violated, a linear mixed model (LMM), a more robust approach, will be employed as an alternative. If needed, additional subgroup analyses may be conducted based on the variables (diagnosis, SPADI severity).
For safety assessment, the incidence of all AEs, regardless of their causal relationship to the treatment, will be tabulated throughout the trial period. Among these, treatment-related adverse events (AEs) will be classified and documented according to each treatment type. The proportion of participants experiencing adverse events (AEs) between each group will be compared using Fisher’s exact test. Finally, changes in laboratory test results will be analyzed using the same approach as that used for effectiveness outcomes.
9. Cost-effectiveness Analysis
An economic evaluation will be run in parallel with the clinical trial26). During the observation period, data on costs and outcomes will be collected from both groups to assess the economic value of the treatment under investigation. The analysis will be performed from a South Korean societal perspective. Cost data will be identified and measured using an economic Case Report Form (eCRF), which comprises a structured questionnaire and is valued based on national health insurance reimbursement rates. Quality of life will be measured using the EQ-5D and valued using a nationally developed tariff27). Utility values and quality-adjusted life years (QALYs) acquired will be calculated using the area under the curve (AUC) method28). Cost and utility data will be analyzed based on the ITT principle. The mechanism of missing data will be assessed, and multiple imputation will be used to handle missing values. For deterministic analysis, mean values of cost and utility will be used to calculate the incremental cost-effectiveness ratio (ICER). A seemingly unrelated regression model and the percentile bootstrapping method will be applied to estimate the sampling uncertainty around the ICER29). Cost-effectiveness planes and cost-effectiveness acceptability curves (CEACs) will also be presented to interpret statistical uncertainty and inform economic decision-making, based on the national willingness-to-pay (WTP) threshold30). Additionally, a decision-analytic modeling approach will be employed to estimate long-term cost-effectiveness beyond the trial period. All analyses will be performed using Stata/MP 19 (StataCorp LLC., College Station, TX, USA).
10. Data and Safety Monitoring
To ensure the safety and integrity of participants’ data, regular monitoring will be conducted in accordance with standard operating procedures. Monitors will evaluate the compliance of study procedures with the study protocol and verify the adequacy of the completed case report forms. Also, adverse events will be assessed to determine whether they are acceptable and whether early termination is necessary. Monitoring visits will be conducted at study start-up, mid-trial, and close-out. The monitoring frequency can be adjusted based on discussions with the researchers.
11. Participant Protections and Ethics
The trial will adhere to general ethical guidelines, including the Declaration of Helsinki and Korean Good Clinical Practice (KGCP). The study protocol was approved by the Institutional Review Board (IRB) of each center: Dongguk University Bundang Hospital (IRB No. DGBOH 2023-0006), Daejeon Korean Medicine Hospital of Daejeon University in Daejeon (IRB No. DJDSKH-23-BM-05), and Kyunghee University Oriental Medicine Center (IRB No. KOMCIRB 2023-06-003-003). Before enrollment, all patients will receive a detailed explanation of the trial and will be asked to sign an informed consent form voluntarily. The consent includes information about the study purpose and procedures, potential risks and benefits, protection of personal information, and responsibilities during the trial.
Discussion
This trial aims to evaluate the therapeutic benefit and cost-effectiveness of DET as an adjunct to AT for patients with shoulder pain. The shoulder joint, being a ball-and-socket joint with multidirectional mobility, is inherently unstable31). This anatomical vulnerability makes it susceptible to injury, resulting in psychological distress, a reduced quality of life, and shoulder pain and functional impairments4). According to TKM clinical practice guidelines, conventional TKM therapies such as AT, electro-AT, CMT, and pharmacopuncture treatment are recommended for the treatment of shoulder pain32). However, the concomitant use of exercise therapy may also serve as a viable treatment strategy, given that shoulder pain is commonly associated with functional impairments, including limited ROM9,10).
Grounded on modern physical principles, exercise therapy applies appropriate force to the body with gradual progression, demonstrating its clinical benefits not only in musculoskeletal pain but also in behavioral aspects33). Currently, various TKM exercise therapies, such as DET, Qigong, and Baduanjin, exist based on traditional life-nourishing theories17,33,34). With growing interest in exercise therapy as an adjunctive treatment option for shoulder pain, several studies have attempted to assess its therapeutic effects15,33). In clinical practice, therapies are currently being used in combination with conventional TKM therapies17–19).
Among them, DET is derived from traditional Daoyin methods, which adopt a holistic perspective, and is combined with therapeutic exercise techniques applied by practitioners15). It restores neuromuscular function through passive or active movements, while maintaining proper body balance through regulated breathing12,15). Furthermore, the personalized breathing techniques during the DET help relieve muscle tightness, promote mental relaxation, and enhance systemic metabolism, reflecting a mind-body holistic approach that distinguishes it from conventional exercise therapies13,14). These effects may be explained by a potential neuropsychological mechanism, highlighting the brain’s role in emotion modulation and the involvement of the hypothalamic-pituitary -adrenal axis in stress regulation35). In addition, the gentle movements of DET, which primarily involve isometric and stretching exercises, effectively minimize physical strain and are thus particularly suitable for older adults16).
Meanwhile, as highlighted in a recent systematic review, there is no convincing evidence regarding the therapeutic effect of DET, due to lack of high-quality evidence from previous trials15). This highlights the need for further well-designed RCTs. In clinical research, RCTs are considered the gold standard for assessing the benefits of a specific intervention due to their inherent advantages, such as randomization and blinding, which help mitigate biases arising from confounding factors. Therefore, we will adopt a rigorous RCT design to evaluate the therapeutic and economic benefits of DET as an add-on therapy. Additionally, since shoulder pain can result from various disorders, symptoms and signs differ among patients, leading to the application of different diagnostic evaluation techniques in clinical practice. Moreover, DET is frequently used as an adjunct to conventional TKM therapies in clinical practice18,19). Taking these into consideration, we adopted a pragmatic approach, selecting DET plus AT as the intervention and AT alone as the comparator. Additionally, we allowed for the selective application of DET techniques and acupoints tailored to individual patients’ symptoms and signs, as well as standard treatment points. This may provide rigorous evidence of the effectiveness of DET in managing shoulder pain, reflecting real clinical practice in TKM.
The application order of DET is scheduled after AT, based on the anticipated anesthetic and muscle-relaxing effects of AT, which are expected to facilitate the concurrent implementation of exercise therapy. Pain itself is recognized as one of the major barriers to adherence for exercise interventions36). The preceding AT is expected to mitigate this barrier, as AT stimulates the nervous system and promotes the release of endogenous substances such as endorphins, thereby inhibiting pain perception37). Furthermore, AT-induced neural signaling is expected to modulate local blood perfusion through the vasodilatory actions of neuropeptides, including substance P and calcitonin gene-related peptide (CGRP)38). This improvement in circulation is expected to alleviate muscle tightness, thereby facilitating the execution of exercise movements. Taken together, these mechanisms are expected to create a more favorable physiological environment for performing DET effectively.
SPADI will be used as the primary outcome of this trial. It is widely used to assess shoulder function, along with other indices such as the Constant-Murley Score (CMS), the Disabilities of the Arm, Shoulder, and Hand (DASH) questionnaire, and the Shoulder Disability Questionnaire. Studies have demonstrated its validity and responsiveness across various shoulder disorders, as well as its simplicity and short administration time39–41). Accordingly, it has been cross-culturally adapted into multiple languages and is widely employed in both clinical and research settings worldwide42,43). Given these advantages and the fact that SPADI is a joint-specific measure focusing on pain and functional aspects related to the shoulder, it is deemed the most appropriate primary outcome measure for this study. Regarding the patient’s quality of life, EQ-5D-5L will be adopted in this trial. The EQ-5D-5L allows more precise measurement of health status at the top of the scale, and captures subtle differences between mild health impairments and full health44). In addition, its low questionnaire burden makes it particularly suitable for follow-up by telephone45). The features of the aforementioned indices are well-aligned with our trial design and are therefore expected to contribute to achieving our aim and obtaining reliable outcomes.
Our study protocol has one limitation: a potentially high risk of performance bias due to the nature of the intervention. Since DET is applied only to the intervention group, patients receiving DET will be instructed to perform specific exercises after AT. Moreover, practitioners will be directly involved in delivering the passive therapeutic techniques. Consequently, both patients and practitioners will inevitably be aware of the treatment allocation. This is a common challenge in trials using exercise or manual therapies, as it is inherently difficult to implement an adequate sham control46). Therefore, we will carry out compensating methods through a blinded assessor, a statistician, and concealed allocation.
Conclusion
This trial is expected to provide evidence on the therapeutic efficacy, safety, and cost-effectiveness of DET in treating patients with shoulder pain. The findings may inform clinicians’ decision-making, supporting DET as a viable adjunctive option for managing shoulder pain. Furthermore, they may contribute to clinical standardization and the development of health insurance policies based on robust scientific evidence.
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