| Literature DB >> 35073897 |
Viviane C Pereira1, Sarah N Silva2, Viviane K S Carvalho3, Fernando Zanghelini3, Jorge O M Barreto3.
Abstract
BACKGROUND: As a source of readily available evidence, rigorously synthesized and interpreted by expert clinicians and methodologists, clinical guidelines are part of an evidence-based practice toolkit, which, transformed into practice recommendations, have the potential to improve both the process of care and patient outcomes. In Brazil, the process of development and updating of the clinical guidelines for the Brazilian Unified Health System (Sistema Único de Saúde, SUS) is already well systematized by the Ministry of Health. However, the implementation process of those guidelines has not yet been discussed and well structured. Therefore, the first step of this project and the primary objective of this study was to summarize the evidence on the effectiveness of strategies used to promote clinical practice guideline implementation and dissemination.Entities:
Keywords: Guideline implementation; Guidelines; Health system
Mesh:
Year: 2022 PMID: 35073897 PMCID: PMC8785489 DOI: 10.1186/s12961-022-00815-4
Source DB: PubMed Journal: Health Res Policy Syst ISSN: 1478-4505
Fig. 1PRISMA flowchart of study selection.
Source: own elaboration
Characteristics of included studies
| Study (article title) | Objective | Number of studies/clinical area | Country/setting | AMSTAR |
|---|---|---|---|---|
| “The effectiveness of interventions designed to increase the uptake of clinical practice guidelines and best practices among musculoskeletal professionals: a systematic review” [ | To summarize and assess evidence about the effectiveness of knowledge translation interventions to improve the uptake and application of clinical practice guidelines and best practices for a wide range of musculoskeletal disorders and healthcare professionals | 11 studies Musculoskeletal disorders | Netherlands, United Kingdom, Australia, United States, Switzerland, Ireland – Setting: NR | Low |
| “A review of quantitative studies of adherence to mental health clinical practice guidelines” [ | To identify and review all published peer-reviewed reports providing quantitative information on rates of adherence to specific mental health guidelines | 41 studies Mental health | United States, United Kingdom, Australia, Scotland, France, Canada – Primary care or other medical clinics, medical centres, nursing homes, acute medical ward, community-based sampling | Critically low |
| “Implementation of treatment guidelines for specialist mental health care” [ | To examine the efficacy of guideline implementation strategies in improving process outcomes (performance of healthcare providers) and patient outcomes and the specific components of different guideline implementation strategies that could influence them | 6 studies Schizophrenia-spectrum disorders | Denmark, German, United States, United Kingdom – Psychiatric units, hospitals | Critically low |
| “Assessing the effectiveness of strategies to implement clinical guidelines for the management of chronic diseases at primary care level in EU member states: a systematic review” [ | To evaluate the effectiveness of strategies for implementing clinical guidelines for chronic disease management in primary care in EU member states | 21 studies Chronic disease | EU member states: Finland, France, Germany, Italy, Spain, Sweden, United Kingdom, Denmark, Netherlands – Primary care level | Low |
| “Health professions digital education on clinical practice guidelines: a systematic review by digital health education collaboration” [ | To evaluate the effectiveness of digital education in improving clinical practice guideline adoption | 17 studies Several areas | Except for one study from an upper-middle-income country, all studies were from high-income countries, with 10 studies from the United States – Setting: NR | Critically low |
| “Evidence-based strategies for implementing guidelines in obstetrics: a systematic review” [ | To determine which strategies have been effective for implementing clinical practice guidelines in obstetric care, and to identify barriers to change and facilitators in obstetrics | 33 studies Obstetric care | Low-, middle- and high-resource settings – Obstetric care | Critically low |
| “Implementing a hospital guideline on pneumonia: a semi-quantitative review” [ | To classify guideline implementation interventions used to improve treatment of community-acquired pneumonia and to quantify the impact of different interventions and their intensity of use on several processes of care and clinical and/or economic outcomes | 27 studies Pneumonia | United States, United Kingdom, Canada, Australia – Hospital setting | Critically low |
| “The effectiveness of computerized clinical guidelines in the process of care: a systematic review” [ | To determine the impact of computerized clinical guidelines on the process of care compared with non-computerized clinical guidelines | 45 studies Acute and chronic | Europe, United States, Oceania – Academic and nonacademic centres | Critically low |
| “Information and communication technologies for the dissemination of clinical practice guidelines to health professionals: a systematic review” [ | To identify studies on the perceived usability and practice behaviour change among health professionals with regard to information and communication technologies for the dissemination of clinical practice guidelines | 21 studies NR | United States, Canada, Europe, and one international study – Setting: NR | Low |
| “A systematic review of the implementation and impact of asthma protocols” [ | To determine the most widely used method of guideline implementation (paper, computer-generated or computerized) reported in the literature, which methods significantly improved clinical care, and the factors most commonly associated with successful and sustainable implementation of asthma guidelines | 104 studies Asthma | United States, United Kingdom, Canada, Australia, Netherlands, Singapore, New Zealand, Brazil, Saudi Arabia, Germany, France, Oman, Switzerland, Italy, Iran, Japan, Taiwan, Korea, Thailand and United Arab Emirates – Outpatients, emergency department and inpatients, patients in other settings | Critically low |
| “Implementing guidelines in nursing homes: a systematic review” [ | To systematically review the effects of interventions for improving the implementation of guidelines in nursing homes | 5 studies Several areas | United States, Germany, Netherlands, Australia, Belgium – Nursing homes | Moderate |
| “Evidence-based guideline implementation in low- and middle-income countries: lessons for mental health care” [ | To investigate studies on the effectiveness of evidence-based clinical practice guideline implementation across physical and mental healthcare in order to inform the provision of mental healthcare in low- and middle-income countries, and to identify transferable lessons from other noncommunicable diseases to mental health | 6 studies Mental healthcare and physical health | Brazil, China, Thailand, Nepal, South Africa and Egypt – General hospitals in urban areas – Primary healthcare centres | Low |
| “Health professionals’ adherence to stroke clinical guidelines: a review of the literature” [ | To review the literature on adherence to clinical guidelines including the impact of adherence on achieving quality indicators for stroke care, and to identify actual and perceived facilitators and barriers with respect to adherence to best practice | 27 studies Stroke care | United States, Australia, United Kingdom, Scotland – National, regional, local and clinical institution level | Critically low |
| “Tools developed and disseminated by guideline producers to promote the uptake of their guidelines” [ | To evaluate the effectiveness of implementation tools developed and disseminated by guideline producers, which accompany or follow the publication of a clinical practice guideline, to promote uptake. Secondarily, to determine which approaches to guideline implementation are most effective | 4 studies Several areas | Netherlands, France, United States and Canada – Private physiotherapy practices, hospitals, family practice | Low |
| “Effectiveness and efficiency of guideline dissemination and implementation strategies” [ | (1) To perform a systematic review of the effectiveness and costs of different guideline development, dissemination and implementation strategies (2) To estimate the resource implications of different development, dissemination and implementation strategies (3) To develop a framework for determining when it is efficient to develop and introduce clinical guidelines based upon the potential costs and benefits of the targeted clinical activity and the effectiveness and costs of guideline development and introduction | 235 studies NR | Most in United States, United Kingdom, Canada, Australia and Netherlands – Primary care, inpatient settings and generalist outpatient or ambulatory care settings, mixed settings, nursing homes or long-term care facilities, emergency departments, specialist outpatient care and a military medical clinic | Low |
| “Implementing practice guidelines for appropriate antimicrobial usage: a systematic review” [ | To identify the best methods for changing prescribing practices and to facilitate better implementation of these guidelines | 40 studies Antimicrobial usage | NR | Critically low |
| “A systematic review of the outcomes of educational interventions relevant to nurses with simultaneous strategies for guideline implementation” [ | To systematically review the literature regarding outcomes of educational interventions relevant to nurses with respect to guideline implementation | 13 studies Several areas | United States, Australia, Iran, Singapore – Nursing units | Critically low |
| “Guideline implementation in allied health professions: a systematic review of the literature” [ | To evaluate the effects of the introduction of clinical guidelines for allied health professionals, and the effectiveness of the guideline dissemination and implementation strategies used | 14 studies NR | United States, Australia, Netherlands, United Kingdom – Clinical institution level, provider level | Critically low |
| “Effectiveness of electronic guideline-based implementation systems in ambulatory care settings – a systematic review” [ | To perform a systematic and comprehensive search of the literature for studies that evaluated the effectiveness of computer-based systems for guideline implementation in ambulatory care settings, with the multidimensionality of the guideline (the guideline had to consist of several aspects or steps) and real-time interaction with the system during consultation as important inclusion criteria | 27 studies Chronic and acute diseases and tobacco use cessation | United States, four in the United Kingdom, five in the Netherlands, two in Norway, one in France, and one in Finland – Ambulatory care, of which four were performed in the emergency department | Low |
| “A systematic review of implementation strategies to deliver guidelines on obstetric care practice in low- and middle-income countries” [ | To evaluate whether strategies for promoting the use of guidelines could improve obstetric practices in low- and middle-income countries | 9 studies Obstetric care | Georgia, Syria, China and Pakistan, Senegal, Mali, Benin, Malawi, Mexico, Thailand, Argentina, Guatemala, India, Pakistan, Kenya and Zambia – Health centres and hospitals, health facilities | Low |
| “Interventions to improve adherence to cardiovascular disease guidelines: a systematic review” [ | To synthesize evidence on the effectiveness of interventions targeting healthcare providers to improve adherence to cardiovascular disease guidelines and patient outcomes | 38 studies Cardiovascular | United States, Netherlands, Italy, England, and Norway, Canada, South Africa, Brazil, Asia–Pacific area and Virgin Islands – Setting: NR | Low |
| “Implementation strategies for guidelines at ICUs: a systematic review” [ | To conduct a systematic review on implementation strategies for clinical practice guidelines in the intensive care unit, in order to assist critical care practitioners in the use of implementation strategies for clinical practice guidelines in the ICU | 8 studies Critical care | Canada, Australia, England and Taiwan, and United States – Adult and neonatal ICUs | Critically low |
| “Use of theory to plan or evaluate guideline implementation among physicians: a scoping review” [ | To summarize current research in the field of guideline implementation to determine whether and how theory has been used to plan or evaluate the implementation and use of guidelines among physicians, as frequent target users of guidelines | 42 studies Several areas | United States, United Kingdom, Australia, Netherlands, Canada, Iran, Belgium, Germany and Saudi Arabia – Setting: NR | Critically low |
| “Educational interventions for implementation of arthritis clinical practice guidelines in primary care: effects on health professional behavior” [ | To evaluate the influence of educational programmes to implement clinical practice guidelines for osteoarthritis and rheumatoid arthritis in primary care | 7 studies Osteoarthritis and rheumatoid arthritis | Country: NR – Primary care environment | Critically low |
| “Improving adherence to guidelines for the diagnosis and management of pelvic inflammatory disease: a systematic review” [ | To examine the strategies that may improve adherence to guidelines for pelvic inflammatory disease diagnosis and management | 3 studies Pelvic inflammatory disease | United States – Hospital and outpatient facilities | Critically low |
| “Systematic review of practice guideline dissemination and implementation strategies for healthcare teams and team-based practice” [ | To synthesize the literature relevant to guideline dissemination and implementation strategies for healthcare teams and team-based practice | 89 studies Not reported | United States and the United Kingdom, Canada, Australia – Setting: NR | Critically low |
| “Enhancing prescribing of guideline-recommended medications for ischaemic heart diseases: a systematic review and meta-analysis of interventions targeted at healthcare professionals” [ | To evaluate whether interventions targeted at healthcare professionals are effective in enhancing prescribing and health outcomes in patients with ischaemic heart diseases | 13 studies Cardiology | North America and Europe – Setting: NR | Low |
| “Interventions to modify health care [provider adherence to asthma guidelines: a systematic review” [ | To determine whether interventions targeting healthcare providers improve adherence to asthma care guidelines and thereby improve outcomes. Healthcare process outcomes such as patients receiving appropriate treatment, and clinical outcomes such as hospitalizations were considered | 68 studies Asthma | Country: NR – Clinical institution level, provider level | Critically low |
| “Effectiveness of implementation interventions in improving physician adherence to guideline recommendations in heart failure: a systematic review” [ | To examine the effectiveness of implementing interventions in increasing physician adherence to the specified heart failure guideline recommendations. Secondarily, to assess the effect of implementation interventions on clinical outcomes, and to identify process and contextual factors that influence implementation success | 38 studies Cardiology | United States, Europe and Australia – Inpatient settings, outpatient settings and mixed settings | Low |
| “Effect of clinical guidelines in nursing, midwifery, and the therapies: a systematic review of evaluations” [ | (1) To identify evaluations in any setting of clinical practice guidelines and related dissemination and implementation strategies in nursing, midwifery, health visiting and other professions allied to medicine, including podiatry, speech and language therapy, physiotherapy, occupational therapy, dietetics, clinical psychology, pharmacy and radiography (2) To estimate the effectiveness and cost-effectiveness of clinical practice guidelines for promoting improved professional practice and enhanced patient outcomes in nursing and professions allied to medicine | 18 studies Pneumococcal and influenza vaccinations, use and follow-up of medications, urinary catheter care | Country: NR – Ambulatory medical practices | Critically low |
| “Implementation of pressure ulcer guidelines: what constitutes a successful strategy?” [ | To identify studies on the effectiveness of strategies in implementing evidence-based guidelines and recommendations for the prevention and/or management of pressure ulcers and the characteristics associated with sustainable implementation of these strategies | 20 studies Pressure ulcer | United States, German, United Kingdom, Australia – Hospitals, nursing homes, community care centres, residential homes, universities, tertiary care hospital, long-term care setting, regional healthcare system | Critically low |
| “Strategies for guideline implementation in primary care focusing on patients with cardiovascular disease: a systematic review” [ | To compare different implementation strategies for guidelines targeting primary or secondary prevention and treatment of cardiovascular diseases | 52 studies Cardiovascular disease | Canada, United States, European countries, Israel, Pakistan and Taiwan – Setting: NR | Critically low |
| “Multifaceted strategies may increase implementation of physiotherapy clinical guidelines: a systematic review” [ | To determine the effectiveness of strategies to increase the implementation of physiotherapy clinical guidelines | 3 studies Physiotherapy clinical | Australia, Netherlands, United Kingdom – Institutional and provider level (physiotherapists) | Critically low |
| “Effectiveness of implementation strategies for clinical guidelines to community pharmacy: a systematic review” [ | To synthesize the literature on the implementation of clinical guidelines in community pharmacy | 22 studies Several areas | Australia, United States United Kingdom, Netherlands, Belgium, Canada, Finland, Germany and Switzerland – Community pharmacy setting | Low |
| “Effects of implementation of psychiatric guidelines on provider performance and patient outcome: systematic review” [ | To summarize the evidence pertaining to the benefits of mental health guidelines with respect to specific implementation strategies | 18 studies Psychiatric | United States, United Kingdom, Denmark and Canada – Primary care, general hospital, specialist mental healthcare settings, mental health clinicians of a managed behavioural healthcare organization | Critically low |
| “Implementing guidelines and innovations in general practice: which interventions are effective?” [ | To evaluate the effectiveness of interventions in promoting the implementation of guidelines and adoption of innovations in general practice | 143 studies NR | United States, United Kingdom, Canada and several other countries – Setting: NR | Critically low |
EU European Union, ICU intensive care unit, NR not reported
Strategies for clinical practice guideline implementation and their definitions
| Category | Strategy | Code | Definition |
|---|---|---|---|
| Coordination of care and management of care processes | Care pathways | CAP | Aim to link evidence to practice for specific health conditions and local arrangements for delivering care [ |
| Coordination of care and management of care processes | Case management | CAM | Introduction, modification or removal of strategies to improve the coordination and continuity of delivery of services, i.e. improving the management of one “case” (patient) [ |
| Coordination of care and management of care processes | Clinical multidisciplinary teams | CMT | Creation of a new team of health professionals of different disciplines or additions of new members to the team who work together to care for patients [ |
| Coordination of care and management of care processes | Communication between providers | CBP | Systems or strategies for improving the communication between healthcare providers, for example systems to improve immunization coverage [ |
| Coordination of care and management of care processes | Continuity of care | COC | Interventions to reduce fragmented care and undesirable consequences of fragmented care, for example by ensuring the responsibility of care is passed from one facility to another so the patient perceives that their needs and circumstances are known to the provider [ |
| Information and communication technology | Information and communication technology | ICT | ICT used by healthcare organizations to manage the delivery of healthcare, and to deliver healthcare [ |
| Changes to the healthcare environment | Structural intervention | SI | Changes to the setting/site of service delivery, physical structure, facilities and equipment, and medical records systems, among others [ |
| Authority and accountability for health policies | Community mobilization | COM | Processes that enable people to organize among themselves [ |
| Interventions targeted at healthcare workers | Academic detailing | AD | Personal visits by a trained person to health workers in their own settings, to provide information with the aim of changing practice [ |
| Interventions targeted at healthcare workers | Audit and feedback | AF | A summary of health workers’ performance over a specified period of time, given to them in a written, electronic or verbal format. The summary may include recommendations for clinical action [ |
| Interventions targeted at healthcare workers | Communities of practice | CP | Groups of people with a common interest who deepen their knowledge and expertise in this area by interacting on an ongoing basis [ |
| Interventions targeted at healthcare workers | Continuous quality improvement | CQI | An iterative process to review and improve care that includes involvement of healthcare teams, analysis of a process or system, a structured process improvement method or problem-solving approach, and use of data analysis to assess changes [ |
| Interventions targeted at healthcare workers | Educational games | EG | The use of games as an educational strategy to improve standards of care [ |
| Interventions targeted at healthcare workers | Educational materials | EMA | Distribution of educational materials to individuals or groups, to support clinical care, i.e. any intervention in which knowledge is distributed [ Distribution of published or printed recommendations for clinical care, including clinical practice guidelines, audiovisual materials and electronic publications. The materials may have been delivered personally or through mass mailings [ |
| Interventions targeted at healthcare workers | Educational meetings | EME | Courses, workshops, conferences or other educational meetings [ |
| Interventions targeted at healthcare workers | Local consensus processes | LCP | Formal or informal local consensus processes, for example agreeing on a clinical protocol to manage a patient group, adapting a guideline for a local health system or promoting the implementation of guidelines [ |
| Interventions targeted at healthcare workers | Local opinion leaders | LOL | The identification and use of identifiable local opinion leaders to promote good clinical practice [ |
| Interventions targeted at healthcare workers | Monitoring the performance of the delivery of healthcare | MP | Monitoring of health services by individuals or healthcare organizations, for example by comparing with an external standard [ |
| Interventions targeted at healthcare workers | Patient-mediated Intervention | PMI | Any intervention aimed at changing the performance of healthcare professionals through interactions with patients, or information provided by or to patients [ |
| Interventions targeted at healthcare workers | Reminders | RE | Manual or computerized interventions that prompt health workers to perform an action during a consultation with a patient, for example computer decision support systems [ |
| Interventions targeted at healthcare workers | Tailored interventions | TI | Interventions to change practice that are selected based on an assessment of barriers to change, for example through interviews or surveys [ |
| Interventions targeted at healthcare organizations | Organizational culture | ORG | Strategies to change organizational culture [ |
| Interventions targeted at healthcare organizations | Financial interventions | FI | Targeted financial incentives for health professionals and healthcare organizations [ |
| Interventions targeted at healthcare workers | Educational intervention | EI | Education-focused intervention [ |
| NA | Patient incentives | PIC | Patient received direct or indirect financial reward or benefit for a specific action or to encourage them to do a specific action [ |
| NA | Patient-directed interventions | PI | Interventions aimed at qualifying patients for self-care and for decision-making [ |
| NA | Administrative restriction | AR | Administrative restrictions related to prescriptions [ |
| NA | Marketing | MKT | Approaches that businesses would normally use to encourage people to use their materials [ |
| NA | Mass media | MM | Varied use of communication that reached great numbers of people including television, radio, newspapers, posters, leaflets and booklets, alone or in conjunction with other interventions; targeted at the population level [ |
| NA | Practice support | PS | Available professional to support the clinical practice or directly to the patient [ |
NA strategies not classified by the EPOC
Effectiveness of guideline implementation strategies from systematic reviews by outcome
| Outcome | ||||||||
|---|---|---|---|---|---|---|---|---|
| Strategy | Process | Professional | Patient | Economic | References | |||
| SS | MS | SS | MS | SS | MS | MS | ||
| RE | ⋄⋄ | ⋄ | ⋄⋄ | ⋄ | ⋄ | ⋄ | [ | |
| EMA | ⋄ | ⋄ | ⋄⋄ | ⋄⋄ | ⋄⋄ | ⋄ | ⋄ | [ |
| EME | ⋄⋄ | ⋄ | ⋄⋄⋄ | ⋄⋄ | ⋄ | ⋄ | ⋄ | [ |
| AF | ⋄⋄ | ⋄⋄ | ⋄⋄⋄ | ⋄ | [ | |||
| CMT | ⋄ | ⋄ | ⋄⋄ | [ | ||||
| LOL | ⋄⋄ | ⋄⋄ | ⋄ | [ | ||||
| CAP | ⋄⋄⋄ | ⋄ | [ | |||||
| PS | ⋄⋄ | ⋄⋄ | ⋄ | [ | ||||
| AD | ⋄ | ⋄ | ⋄ | [ | ||||
| FI | ⋄⋄ | [ | ||||||
| PI | ⋄ | ⋄ | [ | |||||
| COC | ⋄ | [ | ||||||
| ORG | ⋄ | ⋄⋄⋄ | ⋄ | [ | ||||
| SI | ⋄ | ⋄ | [ | |||||
| MP | ⋄⋄ | [ | ||||||
| PMI | ⋄ | ⋄ | [ | |||||
| COM | ⋄ | [ | ||||||
| LCP | ⋄ | ⋄ | [ | |||||
| ICT | ⋄⋄ | [ | ||||||
CAP care pathways, CMT clinical multidisciplinary teams, COC continuity of care, COM community mobilization, ICT information and communication technology, SI structural intervention, AD academic detailing, AF audit and feedback, EMA educational materials, EME educational meetings, LCP local consensus processes, LOL local opinion leaders, MP monitoring the performance of the delivery of healthcare, PMI patient-mediated intervention, RE reminders, ORG organizational culture, FI financial interventions, PI patient-directed interventions, PS practice support, SS single strategy, MS multifaceted strategy
The other strategies did not present ≥ 10 evaluated comparisons and, therefore, the results are presented in Additional file 4
⋄⋄⋄Generally effective (more than two thirds of comparisons in a review demonstrated statistically positive effects)
⋄⋄Mixed effects (one third to two thirds of studies demonstrated statistically positive effects)
⋄Generally ineffective (fewer than one third of studies demonstrated statistically positive effects)
Effectiveness of guideline implementation strategies from meta-analysis by outcome
| Outcome | Process | Patient | ||||
|---|---|---|---|---|---|---|
| Single strategy | Multifaceted strategy | Multifaceted strategy | ||||
| Significant positive result | No statistically significant difference | Significant positive result | No statistically significant difference | Significant positive result | No statistically significant difference | |
| Audit and feedback | - | – | – | – Adherence outcome/long-term (6 studies) [ – Adherence outcome (4 studies)a [ – Adherence outcome (4 studies)a [ – Physician adherence (12 studies) [ | – | – Disease target results in the long term (3 studies) [ |
| Organizational culture | – Physician adherence (14 studies) [ | – | – Physician adherence (17 studies) [ | – | – | – |
| Educational interventions | – Physician adherence (15 studies) [ | – | – Physician adherence (26 studies) [ | – Adherence outcome/short-term (6 studies) [ – Adherence outcome/long-term (8 studies) [ – Adherence outcome (4 studies) [ | – Disease target results in the short term (6 studies) [ – Disease target results in the long term (5 studies) [ | – Mortality in the short term (3 studies) [ – Mortality in the long term (4 studies) [ – Hospitalizations in the long term (4 studies) [ |
| Patient-directed interventions | – Physician adherence (5 studies)a [ | – Physician adherence (5 studies)a [ | – | – Physician adherence(14 studies)a [ – Physician adherence (15 studies)a [ | – | – |
| Reminders | – Physician adherence (15 studies) [ | – | – | – Physician adherence (22 studies) [ – Adherence outcome/long-term (6 studies) [ – Adherence outcome (4 studies) [ | – | – Disease target results in the long term (3 studies) [ |
| Educational meetings | – | – | – | – Adherence outcome/long-term (6 studies) [ – Adherence outcome (4 studies) [ | – | – Disease target results in the long term (3 studies) [ |
| Information and communication technology | – | – | – | – Adherence outcome/long-term (6 studies) [ – Adherence outcome (4 studies) [ | – | – Disease target results in the long term (3 studies) [ |
| Academic detailing | – | – | – | Adherence outcome/long-term (6 studies) [ Adherence outcome (4 studies) [ | – | – Disease target results in the long term (3 studies) [ |
aDifferent outcomes related to physician adherence