Sharing Patient-Controlled Real-World Data Through the Application of the Theory of Commons: Action Research Case Study.

BACKGROUND: Technological advances have radically changed the opportunities for individuals with chronic conditions to practice self-care and to coproduce health care and research. Digital technologies enable patients to perform tasks traditionally carried out by health care professionals in a more convenient way, at lower costs, and without compromising quality. Patients may also share real-world data with other stakeholders to promote individual and population health. However, there is a need for legal frameworks that enable patient privacy and control in such sharing of real-world data. We believe that this need could be met by the conceptualization of patient-controlled real-world data as knowledge commons, which is a resource shared by a group of people. OBJECTIVE: This study aimed to propose a conceptual model that describes how patient-controlled real-world data can be shared effectively in chronic care management, in a way that supports individual and population health, while respecting personal data privacy and control. METHODS: An action research approach was used to develop a solution to enable patients, in a self-determined way, to share patient-controlled data to other settings. We chose the context of cystic fibrosis (CF) care in Sweden, where coproduction between patients, their families, and health care professionals is critical in the introduction of new drugs. The first author, who is a lawyer and parent of children with CF, was a driver in the change process. All coauthors collaborated in the analysis. We collected primary and secondary data reflecting changes during the time period from 2012 to 2020, and performed a qualitative content analysis guided by the knowledge commons framework. RESULTS: Through a series of changes, a national system for enabling patients to share patient-controlled real-world data to different stakeholders in CF care was implemented. The case analysis resulted in a conceptual model consisting of the following three knowledge commons arenas that contributed to patient-controlled real-world data collection, use, and sharing: (1) patient world arena involving the private sphere of patients and families; (2) clinical microsystem arena involving the professional sphere at frontline health care clinics; and (3) round table arena involving multiple stakeholders from different settings. Based on the specification of property rights, as presented in our model, the patient can keep control over personal health information and may grant use rights to other stakeholders. CONCLUSIONS: Health information exchanges for sharing patient-controlled real-world data are pivotal to enable patients, health care professionals, health care funders, researchers, authorities, and the industry to coproduce high-quality care and to introduce and follow-up novel health technologies. Our model proposes how technical and legal structures that protect the integrity and self-determination of patients can be implemented, which may be applicable in other chronic care settings as well.

Implementation of the CDC translational informatics platform--from genetic variants to the national Swedish Rheumatology Quality Register.

BACKGROUND: Sequencing of the human genome and the subsequent analyses have produced immense volumes of data. The technological advances have opened new windows into genomics beyond the DNA sequence. In parallel, clinical practice generate large amounts of data. This represents an underused data source that has much greater potential in translational research than is currently realized. This research aims at implementing a translational medicine informatics platform to integrate clinical data (disease diagnosis, diseases activity and treatment) of Rheumatoid Arthritis (RA) patients from Karolinska University Hospital and their research database (biobanks, genotype variants and serology) at the Center for Molecular Medicine, Karolinska Institutet. METHODS: Requirements engineering methods were utilized to identify user requirements. Unified Modeling Language and data modeling methods were used to model the universe of discourse and data sources. Oracle11g were used as the database management system, and the clinical development center (CDC) was used as the application interface. Patient data were anonymized, and we employed authorization and security methods to protect the system. RESULTS: We developed a user requirement matrix, which provided a framework for evaluating three translation informatics systems. The implementation of the CDC successfully integrated biological research database (15172 DNA, serum and synovial samples, 1436 cell samples and 65 SNPs per patient) and clinical database (5652 clinical visit) for the cohort of 379 patients presents three profiles. Basic functionalities provided by the translational medicine platform are research data management, development of bioinformatics workflow and analysis, sub-cohort selection, and re-use of clinical data in research settings. Finally, the system allowed researchers to extract subsets of attributes from cohorts according to specific biological, clinical, or statistical features. CONCLUSIONS: Research and clinical database integration is a real challenge and a road-block in translational research. Through this research we addressed the challenges and demonstrated the usefulness of CDC. We adhered to ethical regulations pertaining to patient data, and we determined that the existing software solutions cannot meet the translational research needs at hand. We used RA as a test case since we have ample data on active and longitudinal cohort.

Continuous innovation: developing and using a clinical database with new technology for patient-centred care--the case of the Swedish quality register for arthritis.

OBJECTIVE: We describe and explain the development of a clinical quality database and its use for different clinical, management and patient empowerment purposes. DESIGN: A longitudinal case study covering 1993-2009. SETTING: Rheumatology departments in Swedish hospitals. PARTICIPANTS: Those involved in developing the clinical database and its applications and a limited number of users. INTERVENTION(S): Different methods for inputting and storing clinical and patient data and for analysing and presenting the data to providers and patients. MAIN OUTCOME MEASURE(S): Participants' perceptions of the value of different applications and of influences, which helped and hindered the development of the system. RESULTS: Different innovations were introduced at different times continually to increase the ultility of the clinical data and the clinic- and patient coverage of the clinical data system. Limited interview data show postive patient and provider perceptions of the latest application to collect and present data as time trend visual display in the clinical consultation. CONCLUSIONS: A longitudinal perspective revealed how a clinical quality register was developed and how new technologies not imagined in the early 1990s continue to increase the ultility and value of the clinical database. This historical perspective provided limited evidence of impact, but does provide lessons for current strategies for innovation for quality in health care and of the need to consider innovolution processes, rather than discrete innovations, given the rapid pace of change in new technologies. More evidence is needed of the impact of such registers, and of enhancements, on providers and patients and on costs.

Development and psychometric testing of the Swedish version of the Body Awareness Questionnaire.

AIM: This paper is a report of the development and psychometric testing of the Swedish version of the Body Awareness Questionnaire to measure bodily focus of attention. BACKGROUND: The Body Awareness Questionnaire has been identified as an instrument with excellent psychometric properties within the concept of body awareness. It has been used in both research and clinical settings in different contexts. However, a validated Swedish version is not available. METHOD: A cross-sectional design was applied for adaptation of the Body Awareness Questionnaire and psychometric validation. Data were collected between autumn 2009 and spring 2011 from 120 patients diagnosed with rheumatoid arthritis, and from 120 students. The 'concurrent think aloud' method was used in a pre-test to determine the usability of the questionnaire. Cronbach's alpha was used to test the internal consistency, and confirmatory factor analysis was performed to test the construct validity. RESULTS: According to the confirmatory factor analysis, neither the one-factor model nor the four-factor model tested in this study fulfilled the pre-specified criteria in accordance with the Comparative Fit Index, Standardized Root Mean Squared Residual and the Root Mean Square Error of Approximation. The value of Cronbach's alpha for the Swedish version of the Body Awareness Questionnaire was satisfactory. CONCLUSION: Our results indicate that the two models tested in this study do not provide a good fit to the observed data. Further refinement and testing of the Swedish version of the Body Awareness Questionnaire is therefore required. The concept of body awareness may be useful in the management of chronic disease and can be addressed in nursing.

Patients with early rheumatoid arthritis who smoke are less likely to respond to treatment with methotrexate and tumor necrosis factor inhibitors: observations from the Epidemiological Investigation of Rheumatoid Arthritis and the Swedish Rheumatology Register cohorts.

OBJECTIVE: To determine whether cigarette smoking influences the response to treatment in patients with early rheumatoid arthritis (RA). METHODS: We retrieved clinical information about patients entering the Epidemiological Investigation of Rheumatoid Arthritis (EIRA) early RA cohort from 1996 to 2006 (n=1,998) who were also in the Swedish Rheumatology Register (until 2007). Overall, 1,430 of the 1,621 registered patients were followed up from the time of inclusion in the EIRA cohort. Of these, 873 started methotrexate (MTX) monotherapy at inclusion, and 535 later started treatment with a tumor necrosis factor (TNF) inhibitor as the first biologic agent. The primary outcome was a good response according to the European League Against Rheumatism criteria at the 3-month visit. The influence of cigarette smoking (current or past) on the response to therapy was evaluated by logistic regression, with never smokers as the referent group. RESULTS: Compared with never smokers, current smokers were less likely to achieve a good response at 3 months following the start of MTX (27% versus 36%; P=0.05) and at 3 months following the start of TNF inhibitors (29% versus 43%; P=0.03). In multivariate analyses in which clinical, serologic, and genetic factors were considered, the inverse associations between current smoking and good response remained (adjusted odds ratio [OR] for MTX response 0.60 [95% CI 0.39-0.94]; adjusted OR for TNF inhibitor response 0.52 [95% CI 0.29-0.96]). The lower likelihood of a good response remained at later followup visits. Evaluating remission or joint counts yielded similar findings. Past smoking did not affect the chance of response to MTX or TNF inhibitors. Evaluating the overall cohort, which reflects all treatments used, current smoking was similarly associated with a lower chance of a good response (adjusted ORs for the 3-month, 6-month, 1-year, and 5-year visits 0.61, 0.65, 0.78, 0.66, and 0.61, respectively). CONCLUSION: Among patients with early RA, current cigarette smokers are less likely to respond to MTX and TNF inhibitors.

Ten years with biologics: to whom do data on effectiveness and safety apply?

OBJECTIVES: During the past decade, the position of biologics in the therapeutic armamentarium, the number of approved indications and the number of available biologics have changed. Available data on (long-term) safety might thus pertain to patient populations not comparable with contemporary patients. The aim of this study was to assess the extent to which contemporary patients who start or switch biologic therapies are comparable with those patients who gave rise to the currently available data on effectiveness and safety. METHODS: We identified all adult patients with RA (n=9612), PsA (n=1417) and other SpA (n=1652) initiating a first biologic therapy between 1 January 1999 and 31 December 2008, registered in the Swedish Biologics Register (ARTIS), including information on demographics, disease characteristics and 1-year risk of first-line treatment discontinuation. RESULTS: Over calendar time, measures of disease activity at start declined substantially for all indications, and diminished between first-, second- and third-line therapy starts. One-year risks of first-line therapy discontinuation increased. Switchers to anti-TNF and non-TNF biologics had different comorbidities. Despite <50% drug retention at 5 years, most patients remained exposed to some biologic. CONCLUSIONS: The trends in baseline characteristics and drug retention underscores that any effects of biologics, including comparison between different biologics, must be interpreted in light of the characteristics of the population treated. The observed differences further call for continued vigilance to properly evaluate the safety profiles of biologic treatments as they are currently used. Exposure to multiple biologics presents a challenge for attribution of long-term effects.

Feed forward systems for patient participation and provider support: adoption results from the original US context to Sweden and beyond.

BACKGROUND: This is a study of 2 clinical feed forward systems (FFSs) situated in different contexts: in the United States, where the system was developed, and in Swedish clinical settings, where it was first adopted. Both systems were identified as clinically successful despite differing contexts, and the objective of this study is to understand what essential properties determined their success. METHODS: In our search for essential properties of the FFS, we used acceptance, use, and utility as indicators in questionnaires and interviews of patients and providers. Properties were identified as essential if they enabled reinforcing loops favorable for patients, providers, or both at clinical encounters. RESULTS: A total of 44 patients participated in each context, along with 13 providers from the United States and 6 providers from the Swedish clinics. In the patient questionnaire, a majority of patients rated their impression of the FFS as excellent to good (United States: 84%, Sweden: 96%, P < .001). Interviews with both patients and providers indicated that the FFS patient overview displaying structured data previous to the clinical encounter is favorable. These essential properties enabled patient involvement through engagement, education, and communication with the provider, who appreciated them as time-saving for managing data and as decision support. DISCUSSION: Despite distinctly different contexts and locally adapted content, essential properties that induced successful patient participation and provider support were identified as universal in the FFSs. Thus, further spread of the FFS may be enabled to accomplish patient-centered care and improved clinical information and quality management.

System characteristics of healthcare organizations conducting successful improvements.

PURPOSE: In a previous study, based on a survey to all clinical department and primary care center managers in Sweden, it was concluded that the prevailing general improvement strategy is characterized by: drivers for improvement are staff needs; patients and data are not as important; improvements mainly focus on administrative routines and stress management; improvements are mainly reached, by writing guidelines, and conducting meetings; the majority of managers perceive outcomes from this strategy as successful. The purpose of current research in this paper is to investigate whether there is any other improvement strategy at play in Swedish health care. DESIGN/METHODOLOGY/APPROACH: Data from the study of all Swedish managers were stratified into two populations based on an instrument predicting successful improvement. One population represented organizations with exceptionally high probability of successful imrpovement and remaining organizations represented the general improvement strategy. FINDINGS: The paper finds that organizations with high probability for successful change differed from the comparison population at the p = 0.05 level in many of the surveyed characteristics. They put emphasis on patient focus, measuring outcomes, feedback of data, interorganizational collaboration, learning and knowledge, communication/information, culture, and development of administration and management. Thus these organizations center their attention towards behavioral changes supported by data. PRACTICAL IMPLICATIONS: Organizations predicted to conduct successful improvement apply comprehensive improvement strategies as suggested in the literature. Such actions are part of the Patient Centered Task Alignment strategy and it is suggested that this concept has managerial implications as well, as it might be useful in further studies on improvement work in health care. ORIGINALITY/VALUE: This paper provides empirically based findings on a successful improvement strategy that can aid research-informed policy decisions on organizational improvement strategies.

Patient-initiated appointments compared with standard outpatient care for rheumatoid arthritis: a randomised controlled trial.

OBJECTIVES: To test the hypothesis that implementing a patient-initiated system of care could improve clinical outcome in rheumatoid arthritis (RA) using disease activity guided management. METHODS: An 18-month controlled blinded end point two-centre study with 131 patients with RA randomised to intervention (n=64) or control (n=67). The intervention group participants were guaranteed appointments to a rheumatologist within 10 working days if they subjectively experienced a flare in disease activity. The control group participants were booked in advance according to guidelines. Independent assessments were performed in the two groups at 0, 3, 6, 12 and 18 months. Outcome measures included: Disease Activity Score 28 (DAS28), a Visual Analogue Scale (satisfaction with care, confidence in care), number of appointments with a rheumatologist. RESULTS: DAS28 decreased. Median satisfaction and confidence in care were >90 mm on Visual Analog Scale. Median number of appointments was 3. There were no significant differences between the groups among these outcomes. Visits in the intervention group more often resulted in change of treatment than in the control group (p<0.001). CONCLUSIONS: Patient-initiated care was neither better nor inferior to traditional care in terms of outcomes analysed. Patient-initiated appointments can safely be used in everyday outpatient care of RA to empower the patient, if disease activity guided management is applied. Further research should investigate if this intervention can target a subgroup of patients and hence also result in released resources.

The one-person randomized controlled trial.

Currently, the gold standard for collection of clinical evidence is the randomized controlled trial (RCT), preferably with large, multicenter samples of subjects. Although this approach provides valuable information, many clinicians find it difficult to translate RCT results to the individual patient level. In this report, a statistical approach called Design of Experiments (DOE) is described as a method of applying the principles of RCTs one person at a time. An overview of the method, with a simple clinical example, is presented. As shown, DOE is a more efficient method than the sequential approach often taken by clinicians and their patients when evaluating various treatment choices. Further, the effect of multiple interventions can be assessed, alone or in combination with each other. In this way, DOE can be an important addition to the field of evidence-based medicine, although further studies are needed.

Body awareness in persons diagnosed with rheumatoid arthritis.

Living with rheumatoid arthritis (RA) poses physiological and psychological demands on a person. RA is a autoimmune disease that can cause pain, disability, and suffering. The ability to notice bodily inner sensations and stimuli (body awareness, BA) is described in the literature in ways that could have either a positive or a negative impact on a person's health. The concept of BA is complex and a thorough understanding is needed about what BA means from the patient's perspective. This study was therefore conducted to acquire greater insight into this phenomenon. The study is grounded in a phenomenological life-world perspective. Eighteen narrative interviews were conducted in patients (age range 23-78 years) with RA. The interviews were analyzed using the Empirical Phenomenological Psychological method. General characteristics were found running through all 18 interviews, indicating that the disease resulted in a higher degree of negatively toned BA. BA was either a reactive process of searching or controlling after disease-related symptoms or a reactive process triggered by emotions. BA was an active process of taking an inventory of abilities. All participants had the ability to shift focus from BA to the outside world. Four typologies were identified: "A reactive process on symptoms," "A reactive process on emotional triggers," "An active process of taking an inventory of abilities," and "A shifting from BA to the outside world." In conclusion, because BA can be both positively and negatively toned, health care professionals must have a good understanding of when BA is positive and when it is negative in relation to the patient. RA had caused a higher degree of negatively toned BA. Thus, the ability to shift attention from BA to activity in the outside world could sometimes be beneficial for the patient's general health.

Accelerating translational research by clinically driven development of an informatics platform--a case study.

Translational medicine is becoming increasingly dependent upon data generated from health care, clinical research, and molecular investigations. This increasing rate of production and diversity in data has brought about several challenges, including the need to integrate fragmented databases, enable secondary use of patient clinical data from health care in clinical research, and to create information systems that clinicians and biomedical researchers can readily use. Our case study effectively integrates requirements from the clinical and biomedical researcher perspectives in a translational medicine setting. Our three principal achievements are (a) a design of a user-friendly web-based system for management and integration of clinical and molecular databases, while adhering to proper de-identification and security measures; (b) providing a real-world test of the system functionalities using clinical cohorts; and (c) system integration with a clinical decision support system to demonstrate system interoperability. We engaged two active clinical cohorts, 747 psoriasis patients and 2001 rheumatoid arthritis patients, to demonstrate efficient query possibilities across the data sources, enable cohort stratification, extract variation in antibody patterns, study biomarker predictors of treatment response in RA patients, and to explore metabolic profiles of psoriasis patients. Finally, we demonstrated system interoperability by enabling integration with an established clinical decision support system in health care. To assure the usefulness and usability of the system, we followed two approaches. First, we created a graphical user interface supporting all user interactions. Secondly we carried out a system performance evaluation study where we measured the average response time in seconds for active users, http errors, and kilobits per second received and sent. The maximum response time was found to be 0.12 seconds; no server or client errors of any kind were detected. In conclusion, the system can readily be used by clinicians and biomedical researchers in a translational medicine setting.

Innovation as emergence in healthcare: unpacking change from within.

The contemporary healthcare literature suffers from a disproportionate focus on 'given' externally created innovations, and belief in ordered, planned and well-funded implementation processes. As an alternative, the present paper highlights the potential of emergent change processes, using the continuous invention and re-invention of the Rheumatology Quality Registry in Sweden as an example. This 19 year long process, which is still ongoing, does not exhibit the sequential steps that are allegedly determinants of success in the innovation and implementation literature. Yet, it has produced system-wide improvements. We draw on more than 100 informal and formal meetings with practitioners involved in the process studied, observations, documentation analysis and quantitative registry-data. A total of 67 interviews with registry-users and external stakeholders were also performed. The dissipative structures model (complexity theory) was used to analyze the data. The studied process illustrates an ongoing, practice-driven improvement process, which was sparked by abstract and indirect energies that interacted with more concrete innovations such as new drugs. For example, participants tapped new information technologies, changing perspectives and governmental priorities to challenge current ways of working and introduce new ideas. Ideas were realized and spread through various self-organized processes that involved the re-arrangement of existing resources rather than acquisition of new resources. Taken together, these processes brought Swedish rheumatology to new levels of functioning 1992-2011. An important implication of our work is that incremental and practice-driven change processes can significantly transform care systems in the long run. Policy makers need to acknowledge and foster such ongoing innovation processes at micro-level, rather than focusing exclusively on innovations as externally created 'things' that await 'implementation'.

Incidence of rheumatoid arthritis in Sweden: a nationwide population-based assessment of incidence, its determinants, and treatment penetration.

OBJECTIVE: To estimate the nationwide incidence of rheumatoid arthritis (RA) in Sweden, including its variation across age, sex, geography, and demography, and to describe the sensitivity of register-based incidence estimates to different RA case definitions. METHODS: Incident RA patients were identified using the Swedish National Patient Register. In the base case, incident RA was defined as first-ever inpatient or nonprimary outpatient care visit listing an RA diagnosis in 2006-2008, with a second visit listing RA within 1 year. Patients prescribed disease-modifying antirheumatic drugs more than 6 months prior to the first visit listing RA were not regarded as incident. The robustness of this definition was evaluated by more liberal and strict criteria, and by penetration of antirheumatic treatment. RESULTS: Between 2006 and 2008, 8,826 individuals were identified as incident RA patients. The overall incidence was 41 per 100,000 (56 for women, 25 for men). The incidence increased with age and peaked in the 70-79 years age group for both women and men. The age- and sex-standardized incidences were lower in densely populated areas and in individuals with high educational level. No geographic trends were noted. More liberal and strict definitions of RA only altered the observed incidence by approximately 14%. CONCLUSION: The overall nationwide register-based incidence of RA was robust across different case definitions. In a country with universal access to care, RA displayed demographic and socioeconomic, but no geographic, variations in incidence, and peaks at an older age than most commonly reported, with no difference in peak age at RA onset between sexes.

The cost-effectiveness of TNF-inhibitors for the treatment of rheumatoid arthritis in Swedish clinical practice.

OBJECTIVE: The objective was to estimate the cost-effectiveness of TNF-inhibitors for the treatment of rheumatoid arthritis in Swedish clinical practice, both as a first and second biological treatment, with or without the combination of conventional DMARDs. Further sub-group analysis of etanercept treatment was performed. METHODS AND MATERIALS: Patient level data were obtained from three regions of the Swedish Rheumatology Registers. The dataset contained 2,558 patients who had started TNF-inhibitor treatment, 1,049 with etanercept as their first biological treatment. A total of 819 patients had switched to a second TNF-inhibitor, of which 425 to etanercept. A Markov cohort model was used in which health states of disease severity were classified according to HAQ and DAS28. Disease progression and discontinuation rates of TNF-inhibitors were based on the registry and for the comparator on published literature. Mortality, costs and utilities were based on Swedish data. The main analysis had a societal perspective over 20 years and efficacy was measured in quality-adjusted life-years (QALYs). RESULTS: TNF-inhibitor treatment was associated with an increase in QALYs and an incremental cost compared to no biological treatment. The cost per QALY gained with the three TNF-inhibitors ranged from euro 50,000 to euro 120,000, with lower estimates for TNF-inhibitors used in combination with MTX and as a first biologic. At a progression of 0.045 for the comparator, most values remain within the accepted range for cost-effectiveness. CONCLUSIONS: These results demonstrate that the cost per QALY for TNF-inhibitors was higher than in previous assessments based on registry data and that the results were sensitive to the HAQ progression of the comparator.

The medium is the (health) measure: patient engagement using personal technologies.

With the phrase "the medium is the message", Marshall McLuhan argued that technologies are the messages themselves and not just the medium. Almost 50 years later, we understand that modern information and communication technologies expand our ability to perceive our world to an extent that would be impossible without the medium. In this article, we contend that information and communication technologies are becoming the dominant medium for patient engagement. Information and communication technologies will efficiently change patient-reported measurement into much more behaviorally sophisticated information that will create a very different interaction between patients and a new kind of health care workforce.

Managing health care decisions and improvement through simulation modeling.

Simulation modeling is a way to test changes in a computerized environment to give ideas for improvements before implementation. This article reviews research literature on simulation modeling as support for health care decision making. The aim is to investigate the experience and potential value of such decision support and quality of articles retrieved. A literature search was conducted, and the selection criteria yielded 59 articles derived from diverse applications and methods. Most met the stated research-quality criteria. This review identified how simulation can facilitate decision making and that it may induce learning. Furthermore, simulation offers immediate feedback about proposed changes, allows analysis of scenarios, and promotes communication on building a shared system view and understanding of how a complex system works. However, only 14 of the 59 articles reported on implementation experiences, including how decision making was supported. On the basis of these articles, we proposed steps essential for the success of simulation projects, not just in the computer, but also in clinical reality. We also presented a novel concept combining simulation modeling with the established plan-do-study-act cycle for improvement. Future scientific inquiries concerning implementation, impact, and the value for health care management are needed to realize the full potential of simulation modeling.

Effects of GSTM1 in rheumatoid arthritis; results from the Swedish EIRA study.

OBJECTIVE: Glutathione-S-transferases (GSTs) play an important role in tobacco smoke detoxification, interestingly approximately 50% of individuals in most human populations lack the gene GSTM1 due to copy number variation (CNV). We aimed to investigate GSTM1 CNV in Rheumatoid Arthritis (RA) in relation to smoking and HLA-DRB1 shared epitope; the two best known risk factors for RA and in addition, to perform subanalyses in patients where relations between variations in GSTM1 and RA have previously been described. METHODS: qPCR was performed using TaqMan Copy Number assays (Applied Biosystems) for 2426 incident RA cases and 1257 controls from the Swedish EIRA. Odds ratio (OR) together with 95% confidence intervals (CI) was calculated and used as a measure of the relative risk of developing RA. RESULTS: No association between RA and GSTM1 CNV was observed when analyzing whole EIRA. However, ≥1 copy of GSTM1 appears to be a significant risk factor for autoantibody positive RA in non-smoking females ≥60 years (OR: 2.00 95% CI: 1.07-3.74), a population where such relationships have previously been described. Our data further suggest a protective effect of GSTM1 in ACPA-negative smoking men (OR: 0.56 95% CI: 0.35-0.90). CONCLUSION: We assessed the exact number of GSTM1 gene copies in relation to development and severity of RA. Our data provide support for the notion that variations in copy numbers of GSTM1 may influence risk in certain subsets of RA, but do not support a role for GSTM1 CNV as a factor that more generally modifies the influence of smoking on RA.