- Email: [email protected]
Patient acceptable symptomatic state (PASS)
Available online at
www.sciencedirect.com Joint Bone Spine 76 (2009) 321e323
Editorial
Patient acceptable symptomatic state (PASS)
Keywords: Patient acceptable symptomatic state; PASS
Rheumatologists have witnessed radical changes in their everyday practice over the last few years. New imaging studies and diagnostic tests have been introduced and new treatments put on the market. Recommendations and treatment strategies have been developed. Standardized methods have been devised for assessing treatment responses. Evaluation tools, previously reserved for clinical trials, are increasingly used in our everyday practice with the goal of improving quality of care, which requires greater uniformity of clinical practices. Most of the patients managed by rheumatologists experience chronic symptoms, and patient opinion is therefore a crucial component of treatment efficacy assessments. As a result, most of the evaluation criteria used today are patientreported outcome measures (PROs). PROs reflect patients’ perceptions of their health or treatment, as reported by the patients themselves [1]. PROs are, by nature, subjective and are often viewed by clinicians as less reliable than objective criteria. However, PROs are developed using a rigorous scientific procedure. They are accurate, valid, reproducible, and sensitive to change; and they pass the Outcome Measures in Rheumatology (OMERACT) quality filter (truth, discrimination, and feasibility) [2]. PROs are usually numerical and may be analog or multidimensional (e.g., BASDAI and WOMAC) [3,4]. They are used not only in rheumatology, but also in other specialities that deal with chronic disorders. The growing interest in PROs is related to several factors. Chronic diseases for which only symptomatic treatments are available are becoming increasingly prevalent. In several diseases, such as osteoarthritis, no laboratory markers are available for monitoring the patients over time. Even when laboratory markers exist (e.g., in rheumatoid arthritis), the impact on the patient of a change in marker levels may be unclear. For instance, some patients may notice no change in their condition despite increases in their laboratory markers for inflammation. Both physicians and patients need monitoring tools that are relevant to the patient’s experience.
When reading the results of treatment trials, the need for clinically relevant data is obvious. A statistically significant difference between two groups does not necessarily translate into a clinically relevant difference. Yet, it is the clinically relevant effect that may prompt clinicians to change their practice. Let us consider, for instance, a trial in which the pain score on a 100-mm visual analog scale (VAS) showed a 12mm larger decrease in one group than in the other, a statistically significant difference. We need to know what this difference means to the patient. To determine the clinical relevance of a result, attention must shift from the group to the individual, and a clinically relevant scoring system must be devised to convert a continuous quantitative variable (e.g., VAS score) to a binary variable whose meaning is easier to grasp (e.g., success/failure or responder/nonresponder). Instead of the trial results being reported as a difference in the amount of change seen in a variable, they are given as the number of responders in each treatment arm. Importantly, the cutoff chosen to define the two levels of the variable must be clinically relevant. Two treatment-response criteria have been developed based on patients’ perceptions of their health. The minimal clinically important difference or improvement (MCID/I) focuses on the amount of improvement and the Patient acceptable symptomatic state (PASS) on low levels of chronic disease activity, partial remission, and well-being [5,6]. The PASS is the highest symptom level below which patients feel well [7]. At the end of a clinical trial, patients can be classified using the PASS as well or unwell. Responders are patients who achieve the PASS, that is, whose symptoms are less severe than the threshold deemed acceptable. The most widely used external point of reference used to determine the PASS threshold is the reply to the following question: ‘‘Considering the full range of activities you engage in as part of your normal everyday life, your level of pain, and your level of disability, if you were to remain in your present condition for the next few months, would you consider your current health state satisfactory?’’. The best wording of the
1297-319X/$ - see front matter Ó 2009 Elsevier Masson SAS. All rights reserved. doi:10.1016/j.jbspin.2009.03.008
Editorial / Joint Bone Spine 76 (2009) 321e323
322
question and response options (yes/no or Likert scale) is being finalized by the OMERACT working groups. With this question, the VAS pain score threshold is remarkably similar across rheumatic diseases, about 30e40 mm in chronic conditions and slightly less in acute conditions [5,8e11]. The threshold is independent from the baseline pain score in clinical trials, in contrast to MCID/I thresholds. Other studies also found evidence that PASS thresholds were robust. They showed little change with age, disease duration, or gender [8,10]. This stability is very important, as the symptom level considered acceptable at trial initiation must also be acceptable at trial completion. Furthermore, it makes sense to include a time factor in a remission criterion and to incorporate the time one is willing to spend in a given health state into the definition of what is acceptable [12,13]. Among the numerous definitions of a remission suggested for RA (ACR criteria, Pinals’ criteria, and DAS44 and DAS28 thresholds) [14e20], only those developed by Pinals et al. [14] consider the amount of time spent with symptoms, which is set arbitrarily at 2 months or more. The incorporation of time into the PASS is a valuable quality. Finally, and this point is crucial, feeling well is more important to patients than feeling better. Patients report a major improvement only when they perceive their health state as satisfactory, that is, when they achieve the PASS [5,21]. Only then is the improvement relevant. Once the PASS thresholds are defined, they will be helpful in clinical trials for determining the proportion of patients who achieve a satisfactory health status, a measure that reflects the clinical relevance of the treatment effects. Let us consider, as an example, a study of hyaluronic acid in hip osteoarthritis. There was a statistically significant improvement in the VAS pain score, from 51.2 24.9 mm at inclusion to 27.8 20.2 mm after 3 months and 37.0 27.6 mm after 6 months. The proportion of patients who achieved the PASS was 67.7% after 3 months and 60% after 6 months [22]. The PASS can also be used in other conditions; for instance, it proved capable of discriminating between the active drug and the placebo in a study of patients with ankylosing spondylitis [23]. New treatments have led us to set far higher treatment goals, and we can now hope to achieve a remission for patients with chronic rheumatic diseases. The PASS is a valuable tool for assessing these new goals. With the PASS, we can determine how well a treatment attenuates the symptoms to an acceptable and stable level, as perceived by the patients themselves. The criteria used to define a remission, a low disease activity state, minimal disease activity, and the PASS are complementary, as they distinguish different degrees of remission. For instance, the PASS is easier to achieve than a complete remission and is therefore a more common outcome. Thus, rheumatologists can define several symptomatic states that constitute treatment goals and that help to evaluate the relevance of clinical trial results. Conflicts of interest None of the authors has any conflicts of interest to declare.
References [1] U.S. Food and Drug Administration. Guidance for Industry. Patientreported outcome measures: use in medical product development to support labeling claims. Draft guidance. 2006. [2] Boers M, Brooks P, Strand CV, et al. The OMERACT filter for outcome measures in rheumatology. J Rheumatol 1998;25:198e9. [3] Garrett S, Jenkinson T, Kennedy LG, et al. A new approach to defining disease status in ankylosing spondylitis: the Bath ankylosing spondylitis disease activity index. J Rheumatol 1994;21:2286e91. [4] Bellamy N, Buchanan WW, Goldsmith CH, et al. Validation study of WOMAC: a health status instrument for measuring clinically important patient relevant outcomes to antirheumatic drug therapy in patients with osteoarthritis of the hip or knee. J Rheumatol 1988;15:1833e40. [5] Tubach F, Dougados M, Falissard B, et al. Feeling good rather than feeling better matters more to patients. Arthritis Rheum 2006;55:526e30. [6] Tubach F, Ravaud P, Beaton D, et al. Minimal clinically important improvement and patient acceptable symptom state for subjective outcome measures in rheumatic disorders. J Rheumatol 2007;34:1188e93. [7] Kvien TK, Heiberg T, Hagen KB. Minimal clinically important improvement/difference (MCII/MCID) and patient acceptable symptom state (PASS): what do these concepts mean? Ann Rheum Dis 2007;66(Suppl. 3):iii40e1. [8] Heiberg T, Kvien TK, Mowinckel P, et al. Levels of patient acceptable symptom state for disease activity and health status measures in patients with rheumatoid arthritis. Ann Rheum Dis 2007;66(Suppl. II):72. [9] Maksymowych WP, Richardson R, Mallon C, et al. Evaluation and validation of the patient acceptable symptom state (PASS) in patients with ankylosing spondylitis. Arthritis Rheum 2007;57:133e9. [10] Tubach F, Pham T, Skomsvoll JF, et al. Stability of the patient acceptable symptomatic state over time in outcome criteria in ankylosing spondylitis. Arthritis Rheum 2006;55:960e3. [11] Tubach F, Ravaud P, Baron G, et al. Evaluation of clinically relevant states in patient reported outcomes in knee and hip osteoarthritis: the patient acceptable symptom state. Ann Rheum Dis 2005;64:29e33. [12] Boers M, Anderson JJ, Felson DT. Deriving an operational definition of low disease activity state in rheumatoid arthritis. J Rheumatol 2003;30:1112e4. [13] van Riel PL, van Gestel AM. Clinical outcome measures in rheumatoid arthritis. Ann Rheum Dis 2000;59(Suppl. 1):i28e31. [14] Pinals RS, Baum J, Bland J, et al. Preliminary criteria for clinical remission in rheumatoid arthritis. Bull Rheum Dis 1982;32:7e10. [15] Prevoo ML, van Gestel AM, van T Hof MA, et al. Remission in a prospective study of patients with rheumatoid arthritis. American Rheumatism Association preliminary remission criteria in relation to the disease activity score. Br J Rheumatol 1996;35:1101e5. [16] Prevoo ML, van Riel PL, van ’t Hof MA, et al. Validity and reliability of joint indices. A longitudinal study in patients with recent onset rheumatoid arthritis. Br J Rheumatol 1993;32:589e94. [17] Prevoo ML, van ’t Hof MA, Kuper HH, et al. Modified disease activity scores that include twenty-eight-joint counts. Development and validation in a prospective longitudinal study of patients with rheumatoid arthritis. Arthritis Rheum 1995;38:44e8. [18] van der Heijde D, Klareskog L, Boers M, et al. Comparison of different definitions to classify remission and sustained remission: 1 year TEMPO results. Ann Rheum Dis 2005;64:1582e7. [19] van der Heijde DM, van ’t Hof MA, van Riel P, et al. Judging disease activity in clinical practice in rheumatoid arthritis: first step in the development of a disease activity score. Ann Rheum Dis 1990;49:916e20. [20] Pue´chal X. What constitutes remission of rheumatoid arthritis? Joint Bone Spine 2008;75:253e6. [21] Dougados M. It’s good to feel better but it’s better to feel good. J Rheumatol 2005;32:1e2. [22] Rennesson-Rey B, Rat AC, Chary-Valckenaere I, et al. Does joint effusion influence the clinical response to a single Hylan GF-20 injection for hip osteoarthritis? Joint Bone Spine 2008;75:182e8.
Editorial / Joint Bone Spine 76 (2009) 321e323 [23] Dougados M, Luo MP, Maksymowych WP, et al. Evaluation of the patient acceptable symptom state as an outcome measure in patients with ankylosing spondylitis: data from a randomized controlled trial. Arthritis Rheum 2008;59:553e60.
Thao Pham* Assistance Publique e Hoˆpitaux de Marseille (AP-HM), Hoˆpital la Conception, Service de Rhumatologie, 147 bd Baille, 13005 Marseille, France *Corresponding author. Tel.: þ33 4 91 38 34 62; fax: þ33 4 91 38 38 87. E-mail address: [email protected]
323
Florence Tubach Universite´ Paris 7 Denis Diderot, UFR de me´decine, Paris F-75018, France INSERM, U738, Paris, F-75018 France Assistance Publique - Ho´pitaux de Paris (AP-HP), Ho´pital Bichat, De´partement d’Epide´miologie, Biostatistique et Recherche Clinique, Paris F-75018, France 18 March 2009 Available online 13 June 2009
www.sciencedirect.com Joint Bone Spine 76 (2009) 321e323
Editorial
Patient acceptable symptomatic state (PASS)
Keywords: Patient acceptable symptomatic state; PASS
Rheumatologists have witnessed radical changes in their everyday practice over the last few years. New imaging studies and diagnostic tests have been introduced and new treatments put on the market. Recommendations and treatment strategies have been developed. Standardized methods have been devised for assessing treatment responses. Evaluation tools, previously reserved for clinical trials, are increasingly used in our everyday practice with the goal of improving quality of care, which requires greater uniformity of clinical practices. Most of the patients managed by rheumatologists experience chronic symptoms, and patient opinion is therefore a crucial component of treatment efficacy assessments. As a result, most of the evaluation criteria used today are patientreported outcome measures (PROs). PROs reflect patients’ perceptions of their health or treatment, as reported by the patients themselves [1]. PROs are, by nature, subjective and are often viewed by clinicians as less reliable than objective criteria. However, PROs are developed using a rigorous scientific procedure. They are accurate, valid, reproducible, and sensitive to change; and they pass the Outcome Measures in Rheumatology (OMERACT) quality filter (truth, discrimination, and feasibility) [2]. PROs are usually numerical and may be analog or multidimensional (e.g., BASDAI and WOMAC) [3,4]. They are used not only in rheumatology, but also in other specialities that deal with chronic disorders. The growing interest in PROs is related to several factors. Chronic diseases for which only symptomatic treatments are available are becoming increasingly prevalent. In several diseases, such as osteoarthritis, no laboratory markers are available for monitoring the patients over time. Even when laboratory markers exist (e.g., in rheumatoid arthritis), the impact on the patient of a change in marker levels may be unclear. For instance, some patients may notice no change in their condition despite increases in their laboratory markers for inflammation. Both physicians and patients need monitoring tools that are relevant to the patient’s experience.
When reading the results of treatment trials, the need for clinically relevant data is obvious. A statistically significant difference between two groups does not necessarily translate into a clinically relevant difference. Yet, it is the clinically relevant effect that may prompt clinicians to change their practice. Let us consider, for instance, a trial in which the pain score on a 100-mm visual analog scale (VAS) showed a 12mm larger decrease in one group than in the other, a statistically significant difference. We need to know what this difference means to the patient. To determine the clinical relevance of a result, attention must shift from the group to the individual, and a clinically relevant scoring system must be devised to convert a continuous quantitative variable (e.g., VAS score) to a binary variable whose meaning is easier to grasp (e.g., success/failure or responder/nonresponder). Instead of the trial results being reported as a difference in the amount of change seen in a variable, they are given as the number of responders in each treatment arm. Importantly, the cutoff chosen to define the two levels of the variable must be clinically relevant. Two treatment-response criteria have been developed based on patients’ perceptions of their health. The minimal clinically important difference or improvement (MCID/I) focuses on the amount of improvement and the Patient acceptable symptomatic state (PASS) on low levels of chronic disease activity, partial remission, and well-being [5,6]. The PASS is the highest symptom level below which patients feel well [7]. At the end of a clinical trial, patients can be classified using the PASS as well or unwell. Responders are patients who achieve the PASS, that is, whose symptoms are less severe than the threshold deemed acceptable. The most widely used external point of reference used to determine the PASS threshold is the reply to the following question: ‘‘Considering the full range of activities you engage in as part of your normal everyday life, your level of pain, and your level of disability, if you were to remain in your present condition for the next few months, would you consider your current health state satisfactory?’’. The best wording of the
1297-319X/$ - see front matter Ó 2009 Elsevier Masson SAS. All rights reserved. doi:10.1016/j.jbspin.2009.03.008
Editorial / Joint Bone Spine 76 (2009) 321e323
322
question and response options (yes/no or Likert scale) is being finalized by the OMERACT working groups. With this question, the VAS pain score threshold is remarkably similar across rheumatic diseases, about 30e40 mm in chronic conditions and slightly less in acute conditions [5,8e11]. The threshold is independent from the baseline pain score in clinical trials, in contrast to MCID/I thresholds. Other studies also found evidence that PASS thresholds were robust. They showed little change with age, disease duration, or gender [8,10]. This stability is very important, as the symptom level considered acceptable at trial initiation must also be acceptable at trial completion. Furthermore, it makes sense to include a time factor in a remission criterion and to incorporate the time one is willing to spend in a given health state into the definition of what is acceptable [12,13]. Among the numerous definitions of a remission suggested for RA (ACR criteria, Pinals’ criteria, and DAS44 and DAS28 thresholds) [14e20], only those developed by Pinals et al. [14] consider the amount of time spent with symptoms, which is set arbitrarily at 2 months or more. The incorporation of time into the PASS is a valuable quality. Finally, and this point is crucial, feeling well is more important to patients than feeling better. Patients report a major improvement only when they perceive their health state as satisfactory, that is, when they achieve the PASS [5,21]. Only then is the improvement relevant. Once the PASS thresholds are defined, they will be helpful in clinical trials for determining the proportion of patients who achieve a satisfactory health status, a measure that reflects the clinical relevance of the treatment effects. Let us consider, as an example, a study of hyaluronic acid in hip osteoarthritis. There was a statistically significant improvement in the VAS pain score, from 51.2 24.9 mm at inclusion to 27.8 20.2 mm after 3 months and 37.0 27.6 mm after 6 months. The proportion of patients who achieved the PASS was 67.7% after 3 months and 60% after 6 months [22]. The PASS can also be used in other conditions; for instance, it proved capable of discriminating between the active drug and the placebo in a study of patients with ankylosing spondylitis [23]. New treatments have led us to set far higher treatment goals, and we can now hope to achieve a remission for patients with chronic rheumatic diseases. The PASS is a valuable tool for assessing these new goals. With the PASS, we can determine how well a treatment attenuates the symptoms to an acceptable and stable level, as perceived by the patients themselves. The criteria used to define a remission, a low disease activity state, minimal disease activity, and the PASS are complementary, as they distinguish different degrees of remission. For instance, the PASS is easier to achieve than a complete remission and is therefore a more common outcome. Thus, rheumatologists can define several symptomatic states that constitute treatment goals and that help to evaluate the relevance of clinical trial results. Conflicts of interest None of the authors has any conflicts of interest to declare.
References [1] U.S. Food and Drug Administration. Guidance for Industry. Patientreported outcome measures: use in medical product development to support labeling claims. Draft guidance. 2006. [2] Boers M, Brooks P, Strand CV, et al. The OMERACT filter for outcome measures in rheumatology. J Rheumatol 1998;25:198e9. [3] Garrett S, Jenkinson T, Kennedy LG, et al. A new approach to defining disease status in ankylosing spondylitis: the Bath ankylosing spondylitis disease activity index. J Rheumatol 1994;21:2286e91. [4] Bellamy N, Buchanan WW, Goldsmith CH, et al. Validation study of WOMAC: a health status instrument for measuring clinically important patient relevant outcomes to antirheumatic drug therapy in patients with osteoarthritis of the hip or knee. J Rheumatol 1988;15:1833e40. [5] Tubach F, Dougados M, Falissard B, et al. Feeling good rather than feeling better matters more to patients. Arthritis Rheum 2006;55:526e30. [6] Tubach F, Ravaud P, Beaton D, et al. Minimal clinically important improvement and patient acceptable symptom state for subjective outcome measures in rheumatic disorders. J Rheumatol 2007;34:1188e93. [7] Kvien TK, Heiberg T, Hagen KB. Minimal clinically important improvement/difference (MCII/MCID) and patient acceptable symptom state (PASS): what do these concepts mean? Ann Rheum Dis 2007;66(Suppl. 3):iii40e1. [8] Heiberg T, Kvien TK, Mowinckel P, et al. Levels of patient acceptable symptom state for disease activity and health status measures in patients with rheumatoid arthritis. Ann Rheum Dis 2007;66(Suppl. II):72. [9] Maksymowych WP, Richardson R, Mallon C, et al. Evaluation and validation of the patient acceptable symptom state (PASS) in patients with ankylosing spondylitis. Arthritis Rheum 2007;57:133e9. [10] Tubach F, Pham T, Skomsvoll JF, et al. Stability of the patient acceptable symptomatic state over time in outcome criteria in ankylosing spondylitis. Arthritis Rheum 2006;55:960e3. [11] Tubach F, Ravaud P, Baron G, et al. Evaluation of clinically relevant states in patient reported outcomes in knee and hip osteoarthritis: the patient acceptable symptom state. Ann Rheum Dis 2005;64:29e33. [12] Boers M, Anderson JJ, Felson DT. Deriving an operational definition of low disease activity state in rheumatoid arthritis. J Rheumatol 2003;30:1112e4. [13] van Riel PL, van Gestel AM. Clinical outcome measures in rheumatoid arthritis. Ann Rheum Dis 2000;59(Suppl. 1):i28e31. [14] Pinals RS, Baum J, Bland J, et al. Preliminary criteria for clinical remission in rheumatoid arthritis. Bull Rheum Dis 1982;32:7e10. [15] Prevoo ML, van Gestel AM, van T Hof MA, et al. Remission in a prospective study of patients with rheumatoid arthritis. American Rheumatism Association preliminary remission criteria in relation to the disease activity score. Br J Rheumatol 1996;35:1101e5. [16] Prevoo ML, van Riel PL, van ’t Hof MA, et al. Validity and reliability of joint indices. A longitudinal study in patients with recent onset rheumatoid arthritis. Br J Rheumatol 1993;32:589e94. [17] Prevoo ML, van ’t Hof MA, Kuper HH, et al. Modified disease activity scores that include twenty-eight-joint counts. Development and validation in a prospective longitudinal study of patients with rheumatoid arthritis. Arthritis Rheum 1995;38:44e8. [18] van der Heijde D, Klareskog L, Boers M, et al. Comparison of different definitions to classify remission and sustained remission: 1 year TEMPO results. Ann Rheum Dis 2005;64:1582e7. [19] van der Heijde DM, van ’t Hof MA, van Riel P, et al. Judging disease activity in clinical practice in rheumatoid arthritis: first step in the development of a disease activity score. Ann Rheum Dis 1990;49:916e20. [20] Pue´chal X. What constitutes remission of rheumatoid arthritis? Joint Bone Spine 2008;75:253e6. [21] Dougados M. It’s good to feel better but it’s better to feel good. J Rheumatol 2005;32:1e2. [22] Rennesson-Rey B, Rat AC, Chary-Valckenaere I, et al. Does joint effusion influence the clinical response to a single Hylan GF-20 injection for hip osteoarthritis? Joint Bone Spine 2008;75:182e8.
Editorial / Joint Bone Spine 76 (2009) 321e323 [23] Dougados M, Luo MP, Maksymowych WP, et al. Evaluation of the patient acceptable symptom state as an outcome measure in patients with ankylosing spondylitis: data from a randomized controlled trial. Arthritis Rheum 2008;59:553e60.
Thao Pham* Assistance Publique e Hoˆpitaux de Marseille (AP-HM), Hoˆpital la Conception, Service de Rhumatologie, 147 bd Baille, 13005 Marseille, France *Corresponding author. Tel.: þ33 4 91 38 34 62; fax: þ33 4 91 38 38 87. E-mail address: [email protected]
323
Florence Tubach Universite´ Paris 7 Denis Diderot, UFR de me´decine, Paris F-75018, France INSERM, U738, Paris, F-75018 France Assistance Publique - Ho´pitaux de Paris (AP-HP), Ho´pital Bichat, De´partement d’Epide´miologie, Biostatistique et Recherche Clinique, Paris F-75018, France 18 March 2009 Available online 13 June 2009