This work is open access licensed under a Creative Commons Attribution-NonCommercial 4.0 International License, https://creativecommons.org/licenses/by-nc/4.0/Peer reviewe

Ali, Faraz M

Finlay, Andrew

Salek, M Sam

Acta Dermato Venereologica

English

University of Hertfordshire Research Archive

Research ArchiveCitation for published version:Faraz M. ALI, M. Sam SALEK, and Andrew Y. FINLAY, ‘Two Minimal Clinically Important Difference (2MCID): A New Twist on an Old Concept’, Acta Dermato-Venereologica, Vol. 98(7): 715-717, (2018).DOI:https://doi.org/10.2340/00015555-2894Document Version:This is the Published Version.  Copyright and Reuse: © 2018 Acta Dermato-Venereologica.This is an open access article under the CC BY-NC 4.0 licensehttps://creativecommons.org/licenses/by-nc/4.0/EnquiriesIf you believe this document infringes copyright, please contact Research & Scholarly Communications at rsc@herts.ac.ukActaDVActaDVAdvances in dermatology and venereologyActa Dermato-VenereologicaSHORT COMMUNICATIONActa Derm Venereol 2018; 98: 715–717This is an open access article under the CC BY-NC license. www.medicaljournals.se/actaJournal Compilation © 2018 Acta Dermato-Venereologica.doi: 10.2340/00015555-2894715The minimal clinically important difference (MCID) is a widely used concept to interpret the meaning of health-related quality of life (HRQoL) score changes. However, to give a greater sense of the meaning of score change across a wider spectrum of score changes, we propose a new concept of ‘2MCID’. This represents a score change of twice the MCID. This approach, novel in dermatology, has been used in other areas (1, 2) and highlights therapies that reach this higher change thres-hold. We hypothesise that this method would better dis-criminate between the efficacy of interventions to help guide clinical judgement and patient progress. HRQoL outcome measures capture several aspects of a patient’s overall well-being (3). Such measures are increasingly being implemented in interventional studies alongside clinical objective parameters as important contributors towards morbidity and mortality data (4). Reports of studies often include HRQoL data citing statistical differences pre- and post-intervention, though statistically significant changes may not be reflective of meaningful change in HRQoL, particularly within large sample sizes which may produce statistically significant change despite the change being small (5).The MCID is the minimum difference needed for a patient to perceive the change as beneficial (6) and may be used to determine whether a medical intervention improves patient perceived outcomes. Factors to consi-der when calculating the MCID for a particular outcome include: patient baseline severity, particular disease or condition, patient demographics and treatment. There is no consensus on the best methodology for calculating the MCID (7), and values may therefore differ. Despite these limitations, it is still more useful for clinicians to assess intervention effectiveness based on the patient’s perspective, rather than solely on statistical significance. The most commonly utilized quality of life (QoL) tool in psoriasis trials is the Dermatology Life Quality Index (DLQI), with an MCID of 4 points (8, 9). During this systematic review we noted that multiple MCID could provide a further aid to the results’ interpretation: we felt this novel concept deserved further exploration. We have therefore applied the 2MCID concept to data from that review (8).METHODSA systematic review was presented by Ali et al. (8). We have introduced the concept of 2MCID to that dataset (i.e. DLQI score change of at least 8) to demonstrate comparative efficacy between interventions.RESULTSA total of 100 trials were identified by the systematic review, covering diverse interventions. As the DLQI was the most commonly used QoL measure (83% of studies), the 2MCID concept was tested on interventions with documented DLQI scores. Fig. 1 summarises all the interventions that met the different MCID thresholds.For topical treatments, clobetasol 0.05% spray showed the greatest improvement at 4 weeks (2MCID, 8 point im-provement), followed by calcipotriol plus betamethasone at 8 weeks (6.4 points). These changes are comparable to ustekinumab 90 mg at 12 weeks (mean 2MCID (8 point) improvement) and ciclosporin 3–5 mg/kg at 12 weeks (6.6 point improvement). No other topical therapy reached 2MCID. However, it is important to consider the context of baseline psoriasis severity, treatment duration and long-term QoL maintenance. Methotrexate 15 mg at 16 weeks was the only systemic intervention over the 2MCID threshold (8.7 points). This was comparable to several biologics, including etaner-cept 50 mg at 24 weeks and ustekinumab 90 mg at 12 weeks (8.7 points). Infliximab 5 mg/kg at 16 weeks and secukinumab 300 mg at 12 weeks demonstrated the largest improvement in DLQI score of a mean of 11.4 (>2MCID), just short of 3MCID. Amongst other interventions, an energy-res-tricted diet with immunosuppressive therapy at 24 weeks recorded DLQI improvement of 14.4 (3MCID). DLQI at 12 weeks improved by 11.2 (>2MCID) with PUVAsol 0.6 mg/kg + isotretinoin 0.5 mg/kg: for PUVAsol alone, DLQI improvement was 6.8.For studies with treatment endpoint and assessment at 12 weeks, the interventions with the greatest mean DLQI impact in each category were secukinumab 300 mg (2MCID, 11.4 points), ciclosporin 3–5 mg/kg (1MCID, 6.6 points), PUVAsol 0.6 mg/kg+isotretinoin 0.5 mg/kg (2MCID, 11.2 points), Liquor Carbonis Distillate solution 15% (1MCID, 5.8 points) and educational pro-gramme (1MCID, 4 points). DISCUSSIONPreviously, Leaf & Goldfarb (1) described the impact of erythropoiesis stimulating agents on HRQoL using Short-Two Minimal Clinically Important Difference (2MCID): A New Twist on an Old Concept Faraz M. ALI1, M. Sam SALEK2,3 and Andrew Y. FINLAY11Department of Dermatology and Wound Healing, Division of Infection and Immunity, School of Medicine, College of Biomedical and Life Sciences, Cardiff University, Cardiff, 2School of Life and Medical Sciences, University of Hertfordshire, Hatfield, and 3Institute for Medicines Development, Cardiff, UK.Accepted Jan 23, 2018; Epub ahead of print Jan 24, 2018ActaDVActaDVAdvances in dermatology and venereologyActa Dermato-VenereologicaShort communication716www.medicaljournals.se/actaForm 36 and The Kidney Disease Questionnaire. However, the authors only infrequently arbitrarily refer to score changes using multiples of MCID without formal concept utilization. Similarly, Jones et al. (2) equate a change of ‘twice the MCID’ to a ‘large benefit’ when comparing active treatments for COPD against placebo using the St. George’s Respiratory Questionnaire. Neither study formally explored or stratified results.Although score banding descriptors can be used (10) to describe patient numbers within score bands pre- and post-intervention, a method is needed to discriminate between the extent of the effect of interventions on QoL. The concept of ‘multiple-MCID’ could add meaning to score change when comparing therapies, or when com-paring results across different QoL instruments as a ‘unit of change’. 2MCID appears to be a practi-cal threshold providing a meaningful ‘hurdle’ that developers of new interventions might strive to achieve. In the systematic review analysis, only one data set from 83 RCTs demonstrated a change of 3MCID, indicating that a 3MCID ‘hurdle’ would be a difficult and impractical threshold.This ‘pilot study’ of the ‘multiple-MCID’ con-cept demonstrates the potential benefit of compa-ring the extent of impact of different categories of interventions on QoL and interpreting change over time. We have demonstrated that some systemic interventions may impact QoL to the same extent as certain biologic treatments. Similarly, certain topical treatments may be as efficacious as syste-mic alternatives. However, the systematic review dataset is not homogenous and often patients have different baseline severities. Although MCID values are applied across a spectrum of scores in interpreting change in scores of a measure, in reality the MCID score value may be different if the score change is at the lower or upper end of a HRQoL measure score range. This criticism of the concept of MCID requires further investiga-tion, possibly through meta-regression where the magnitude of effect on DLQI is regressed on baseline severity. The 2MCID concept may be too simplistic: ideally the identification and calculation of a multiple-MCID score should be based on prospective research based on patient assessment of a higher level of change, using an anchor question based on, say, “Major clinically important difference”. Despite these reservations we believe ‘multiple-MCID’ provides additional meaningful informa-tion on clinical improvement and may be of value to clinicians, patients and the pharmaceutical industry. Medications that meet the ‘2MCID’ minimum threshold might be more readily appro-InterventionYinxieling formula at 8 weeksXP-828L (Dermylex) 400 mg at 8 weeksVoclosporin 0.4 mg/kg at 12 weeksVoclosporin 0.3 mg/kg at 12 weeksVoclosporin 0.2 mg/kg at 12 weeksVoclosporin (ISA247) 1.5 mg/kg at 12 weeksVoclosporin (ISA247) 0.5 mg/kg at 12 weeksUstekinumab 90 mg at 24 weeksUstekinumab 90 mg at 12 weeksUstekinumab 45 mg at 24 weeksUstekinumab 45 mg at 12 weeksUstekinumab 45-90 mg with immediate methotrexate withdrawal at 16 weeksTriamcinolone Acetonide 0.1% at 8 weeksTofacitinib 5 mg at 12 weeksTofacitinib 2 mg at 12 weeksTofacitinib 15 mg at 12 weeksSulphurous Mineral Waters Spray at 2 weeksSecukinumab 300 mg at 12 weeksSecukinumab 150 mg at 12 weeksPUVAsol 0.6 mg/kg at 12 weeksPUVAsol 0.6 mg/kg & Isotretinoin 0.5 mg/kg at 12 weeksPlacebo + nUVB at 24 weeks (compared with Methotrexate + nUVB)Mometasone furoate 0.1% at 1 weekMometasone furoate 0.1% + salicylic acid 5% at 1 weekMindfulness-based cognitive therapy at 8 weeksMethotrexate 7.5 mg at 16 weeksMethotrexate 7.5 mg at 12 weeksMethotrexate 15 mg at 16 weeksMethotrexate 15 mg + nUVB at 24 weeksMethotrexate + Folic Acid 5 mg at 12 weeksMethotrexate (without Folic Acid) at 12 weeksLow energy diet at 16 weeksLow Dose Cytokines at 12 weeksLiraglutide 1.8 mg at 8 weeksLeflunomide 20 mg at 24 weeksLCD Solution 15% at 12 weeksIxekizumab 75 mg at 8 weeksIxekizumab 25 mg at 8 weeksIxekizumab 150 mg at 8 weeksItolizumab 1.6 mg/kg at 12 weeksInterdisciplinary dermatological and psychiatric care for psoriasis at 24 weeksInfliximab 5 mg/kg at 50 weeksInfliximab 5 mg/kg at 24 weeksInfliximab 5 mg/kg at 16 weeksInfliximab 5 mg/kg at 14 weeksInfliximab 5 mg/kg at 10 weeksInfliximab 5 mg/kg at 100 weeksInfliximab 3 mg/kg at 50 weeksInfliximab 3 mg/kg at 10 weeksEtanercept 50 mg at 54 weeksEtanercept 50 mg at 24 weeksEtanercept 50 mg at 12 weeksEtanercept 50 mg + nUVB at 12 weeks (Patients who did not achieve PASI 90 after 12 weeks of Etanercept)Etanercept 25 mg at 54 weeksEtanercept 25 mg at 12 weeksEtanercept 25 mg + continued methotrexate treatmentEtanercept 100 mg at 12 weeksEtanercept + tapered methotrexateEnergy-restricted diet at 24 weeksEfalizumab 1 mg/kg at 12 weeksEducational Programme at 12 weeksEducational Nursing Intervention at 6 weeksDermatological care for psoriasis at 24 weeksDAB389IL-2 (5-15 mg/kg) at 4 weeksClobetasol Spray 0.05% at 4 weeksClobetasol Foam 0.05% at 2 weeksClobetasol Cream 0.05% at 2 weeksCiclosporin 3-5 mg/kg at 12 weeksChondroitin sulphate 800 mg at 12 weeksCertolizumab 400 mg at 24 weeksCertolizumab 400 mg at 12 weeksCertolizumab 200 mg at 24 weeksCertolizumab 200 mg at 12 weeksCalcipotriol betamethasone at 8 weeksCalcipotriol betamethasone at 4 weeksCalcipotriol at 4 weeksCalcipotriol 50 mcg/g at 8 weeksCalcipotriene 0.005% at 12 weeksBrodalumab 70 mg at 12 weeksBrodalumab 280 mg at 12 weeksBrodalumab 210 mg at 12 weeksBrodalumab 140 mg at 12 weeksBriakinumab 200 mg at 12 weeksBriakinumab 100 mg at 40 weeksBetamethasone valerate dressing at 4 weeksBetamethasone at 8 weeksAuricular Therapy + Yinxieling formula at 8 weeksApremilast 30 mg at 16 weeksApremilast 20 mg at 16 weeksApremilast 10 mg at 8 weeksAloe Vera 70% at 8 weeksAlefacept 15 mg at 16 weeksAlefacept 15 mg at 12 weeksAlefacept 10 mg at 12 weeksAdalimumab 80 mg at 24 weeksAdalimumab 40 mg at 24 weeksAdalimumab 40 mg at 16 weeksAdalimumab 40 mg at 12 weeksAdalimumab 40 mg + vehicle at 16 weeksAdalimumab 40 mg + calcipotriol betamethasone at 16 weeksChange in DLQI score from baseline7.06.05.04.03.02.01.0 .0-1.0-2.0-3.0-4.0-5.0-6.0-7.0-8.0-9.0-10.0-11.0-12.0-13.0-14.0-15.02MCID1 MCIDFig. 1. Mean Dermatology Life Quality Index (DLQI) score change in 83 clinical trials for psoriasis (8), showing those interventions that reached 1 minimal clinically important difference (MCID) and 2 MCID score change.ActaDVActaDVAdvances in dermatology and venereologyActa Dermato-Venereologica717Short communicationActa Derm Venereol 2018ved by pharmaceutical regulatory authorities and health technology assessment agencies. This concept may also enable researchers to better distinguish between inter-ventions and comparators in trials, potentially improving patients’ access to the most effective new medicines. Prospective longitudinal studies could aim to prove the usefulness of the concept before implementing it more widely. Further work is required before this novel concept is adopted in treatment decision-making and in reimbursement appraisals.REFERENCES1. Leaf DE, Goldfarb DS. Interpretation and review of health-related quality of life data in CKD patients receiving treatment for anemia. Kidney Int 2008; 75: 15–24.2. Jones PW, Gelhorn H, Wilson H, Karlsson N, Menjoge S, Mül-lerova H, et al. Responder analyses for treatment effects in COPD using the St George’s Respiratory Questionnaire. Chronic Obstr Pulm Dis 2017; 4: 124.3. Revicki DA, Osoba D, Fairclough D, Barofsky I, Berzon R, Leidy N, et al. Recommendations on health-related quality of life research to support labeling and promotional claims in the United States. Qual Life Res 2000; 9: 887–900.4. Crosby RD, Kolotkin RL, Williams GR. Defining clinically meaningful change in health-related quality of life. J Clin Epidemiol 2003; 56: 395–407.5. Osoba D, Rodrigues G, Myles J, Zee B, Pater J. Interpreting the significance of changes in health-related quality-of-life scores. J Clin Oncol 1998; 16: 139–144.6. Jaeschke R, Singer J, Guyatt GH. Measurement of health sta-tus: ascertaining the minimal clinically important difference. Control Clin Trials 1989; 10: 407–415.7. Gatchel RJ, Lurie JD, Mayer TG. Minimal clinically important difference. Spine 2010; 35: 1739–1743.8. Ali F, Cueva A, Vyas J, Atwan A, Salek M, Finlay A, et al. A systematic review of the use of quality-of-life instruments in randomized controlled trials for psoriasis. Br J Dermatol 2017; 176: 577–593.9. Basra MKA, Salek MS, Camilleri L, Sturkey R, Finlay AY. Determining the minimal clinically important difference and responsiveness of the Dermatology Life Quality Index (DLQI): further data. Dermatology 2015; 230: 27–33.10. Hongbo Y, Thomas CL, Harrison MA, Salek MS, Finlay AY. Translating the science of quality of life into practice: What do dermatology Life Quality Index Scores Mean? J Invest Dermatol 2005; 125: 659–664.

Two Minimal Clinically Important Difference (2MCID) : A New Twist on an Old Concept

F Ali

M Salek

A Finlay

Crossref

Two Minimal Clinically Important Difference (2MCID): A New Twist on an Old Concept

Ali, Faraz

Salek, M. S.

Online Research @ Cardiff

This is a n  Op e n  Acces s  doc u m e n t  dow nloa d e d  fro m  ORCA, Ca r diff U nive r si ty 'sins ti t u tion al r e posi to ry: h t t p s://o rc a .c a r diff.ac.uk/id/e p rin t/10 9 0 4 2/This  is t h e  a u t ho r’s ve r sion  of a  wo rk  t h a t  w as  s u b mi t t e d  to  / a c c e p t e d  forp u blica tion.Cit a tion  for  final p u blish e d  ve r sion:Ali, Fa r az,  S alek,  M.  S. a n d  Finlay, Andr e w  ORCID: h t t p s ://o rcid.o r g/000 0-0 0 0 3-2 1 4 3-1 6 4 6  2 0 1 8.  Two mi nim al clinically impor t a n t  diffe r e nc e  (2MCID): An e w  t wis t  on  a n  old  conc e p t .  Acta  De r m a to  Vene r eologica  9 8  (7) , p p.  7 1 5-7 1 7.1 0.2 3 4 0/0 00 1 5 5 5 5-2 8 9 4  file P u blish e r s  p a g e:  h t t p://dx.doi.or g/10.23 4 0/000 1 5 5 5 5-2 8 9 4< h t t p://dx.doi.o rg/10.23 4 0/000 1 5 5 5 5-2 8 9 4 >Ple a s e  no t e:  Ch a n g e s  m a d e  a s  a  r e s ul t  of p u blishing  p roc e s s e s  s uc h  a s  copy-e di ting,for m a t ting  a n d  p a g e  n u m b e r s  m ay no t  b e  r eflec t e d  in t his  ve r sion.  For  t h ed efini tive  ve r sion  of t his  p u blica tion,  ple a s e  r ef e r  to  t h e  p u blish e d  sou rc e.  Youa r e  a dvise d  to  cons ul t  t h e  p u blish e r’s ve r sion  if you  wish  to  ci t e  t his  p a p er.This ve r sion  is b ein g  m a d e  av ailable  in  a cco r d a n c e  wit h  p u blish e r  policie s.S e e  h t t p://o rc a .cf.ac.uk/policies.h t ml for  u s a g e  policies.  Copyrigh t  a n d  m o r al  r i gh t sfor  p u blica tions  m a d e  available  in ORCA a r e  r e t ain e d  by t h e  copyrig h thold e r s .117461  2MCID (Two Minimal Clinically Important Difference): a new twist on an old concept  Ali FM1, Salek MS2, 3, Finlay AY1  1Department of Dermatology and Wound Healing, Division of Infection and Immunity, School of Medicine, College of Biomedical and Life Sciences, Cardiff University, Cardiff, UK  2School of Life and Medical Sciences, University of Hertfordshire, Hatfield, UK 3Institute for Medicines Development, Cardiff, UK.  Introduction The minimal clinical important difference (MCID) is a useful and widely used concept to interpret the meaning of health-related quality of life (HRQoL) score changes. However, in order to give a greater sense of the meaning of score change across a wider spectrum of score changes, we propose a new concept of ‘2MCID’. This represents a score change of twice the MCID. This approach, novel in dermatology, has been used in other areas (1, 2) and highlights therapies that reach this higher change threshold. We hypothesise that this method would better discriminate between the efficacy of interventions to help guide clinical judgment and patient progress.   HRQoL outcome measures are holistic, multi-faceted tools that capture several aspects of a patient’s overall well-being (3). Such measures are increasingly being implemented in interventional studies alongside clinical objective parameters as important contributors towards morbidity and mortality data (4). Reports of studies often include HRQoL data citing statistical differences pre- and post-intervention, though statistically significant changes may not be truly reflective of meaningful change in HRQoL, particularly within large sample sizes which may produce statistically significant change despite the change being small. (5) The MCID is described as the minimum difference needed for a patient to perceive the change as beneficial (6) and may be used to determine whether a medical intervention improves patient perceived outcomes. Factors to consider when calculating the MCID for a particular outcome include: patient baseline severity, particular disease or condition, patient demographics and treatment. As a result, there is no consensus on the best methodology for calculating the MCID (7), and values may therefore differ within the same population. Despite these limitations, it is still considered more useful for clinicians to assess the effectiveness of an intervention based on the patient’s perspective, rather than solely on statistical significance.  Our recent systematic review demonstrated that the most commonly utilized QoL tool in dermatological trials is the Dermatology Life Quality Index (DLQI), with an MCID of 4 points (8, 9). While carrying out this systematic review it appeared that multiple MCID could provide a further aid to the interpretation of the results and we felt that this novel concept deserved further exploration. We have therefore applied the concept of 2MCID to data summarized in that review (8).  Methods A systematic review was presented by Ali et al (8). We have introduced the concept of 2MCID to that dataset (i.e. DLQI score change of at least 8) to demonstrate comparative efficacy between interventions.  Results A total of 100 trials were identified by the systematic review, covering a diverse range of interventions. As the DLQI was the most commonly used QoL measure (83% of studies), the 2MCID concept was tested on interventions with documented DLQI scores. Figure 1 summarises all the interventions that met the different MCID thresholds. For topical treatments, clobetasol 0.05% spray showed the greatest improvement at 4 weeks (2MCID, 8 point improvement), followed by calcipotriol plus betamethasone at 8 weeks (6.4 points). These changes are comparable to ustekinumab 90 mg at 12 weeks (average 2MCID (8 point) improvement) and ciclosporin 3-5 mg/kg at 12 weeks (6.6 point improvement). No other topical therapy reached 2MCID. However, it is important to consider the context of baseline psoriasis severity, treatment duration and long-term QoL maintenance.  Methotrexate 15 mg at 16 weeks was the only systemic intervention over the 2MCID threshold (8.7 points). This was comparable to several biologics, including etanercept 50 mg at 24 weeks and ustekinumab 90 mg at 12 weeks (8.7points).   Infliximab 5 mg/kg at 16 weeks and secukinumab 300 mg at 12 weeks on average demonstrated the largest improvement in DLQI score of 11.4 (>2MCID), just short of 3MCID. Amongst other interventions, an energy-restricted diet with immunosuppressive therapy at 24 weeks recorded DLQI improvement of 14.4 (3MCID). DLQI at 12 weeks improved by 11.2 (>2MCID) with PUVAsol 0.6 mg/kg + isotretinoin 0.5 mg/kg: for PUVAsol alone, DLQI improvement was 6.8.  For studies with treatment endpoint and assessment at 12 weeks, the interventions with the greatest average DLQI impact in each category were secukinumab 300 mg (2MCID, 11.4 points), ciclosporin 3-5 mg/kg (1MCID, 6.6 points), PUVAsol 0.6 mg/kg + isotretinoin 0.5 mg/kg (2MCID, 11.2 points), Liquor Carbonis Distillate solution 15% (1MCID, 5.8 points) and educational programme (1MCID, 4 points).    Discussion Previously, Leaf and Goldfarb (1) described the impact of erythropoiesis stimulating agents (ESAs) on HRQoL using Short-Form 36 (SF-36) and The Kidney Disease Questionnaire (KDQ). However, the authors only infrequently and arbitrarily refer to score changes for these measures using multiples of MCID without formal utilization of the concept. Similarly, Jones, Gelhorn (2) equate a change of ‘twice the MCID’ to a ‘large benefit’ when comparing active treatments for COPD against placebo using the St. George's Respiratory Questionnaire (SGRQ). However, neither study formally explored or stratified results using this concept.  Although it is possible to apply score banding descriptors (10) to describe the number of patients within each score band pre and post intervention, there needs to be a method that can discriminate between the extent of the effect of interventions on QoL. The concept of ‘multiple-MCID’ could add meaning to score change when comparing therapies, and possibly when comparing results across different QoL instruments as a ‘unit of change’. The question may arise as to why 2MCID should be chosen rather than other multiples. 2MCID appears to be a practical threshold providing the potential of a meaningful ‘hurdle’ that developers of new interventions might strive to achieve. As indicated in the analysis of the systematic review, only one out of a hundred RCTs demonstrated a change of 3MCID indicating that a 3MCID ‘hurdle’ would be a difficult and impractical threshold to achieve.   This ‘pilot study’ of the concept of ‘multiple-MCID’ demonstrates the potential benefit of comparing the extent of impact of different categories of interventions on QoL and interpreting change over time. For example, we have demonstrated that certain systemic interventions may impact QoL to the same extent as certain biologic treatments. Similarly, certain topical treatments may be as efficacious as systemic alternatives. Interpretation of these conclusions, however, should take into account that the dataset of the systematic review is not homogenous and often patients have different baseline severities. Furthermore, although MCID values are applied across a spectrum of scores in interpreting change in scores of a measure, in reality the MCID score value may be different depending on whether the score change is at the lower or upper end of a HRQoL measure score range. This criticism of the concept of MCID requires further investigation. One way to explore this would be through meta-regression where the magnitude of effect on DLQI is regressed on baseline severity. The concept of 2MCID may be too simplistic: ideally the identification and calculation of a multiple-MCID score should be based on prospective research that takes into account patient assessment of a higher level of change, using an anchor question based on, say, “Major clinically important difference”.   Despite these reservations and investigation suggestions, as a ‘proof of concept’ we believe ‘multiple-MCID’ provides additional meaningful information on clinical improvement and may be of value to clinicians, patients and the pharmaceutical industry. For example, medications that meet the ‘2MCID’ minimum threshold might be more easily approved by both pharmaceutical regulatory authorities and health technology assessment (HTA) agencies. This concept may also enable researchers to distinguish more efficiently between interventions and comparators in trials, potentially improving patients’ access to the most effective new medicines. Prospective longitudinal studies could aim to prove the usefulness of the concept before implementing it on a broader scale. Further work is required before this novel concept is adopted in treatment decision-making and in reimbursement appraisals.    REFERENCES  1. Leaf DE, Goldfarb DS. Interpretation and review of health-related quality of life data in CKD patients receiving treatment for anemia. Kidney Int 2008; 75: 15-24. 2. Jones PW, Gelhorn H, Wilson H, Karlsson N, Menjoge S, Müllerova H, et al. Responder analyses for treatment effects in COPD using the St George’s Respiratory Questionnaire. Chronic Obstr Pulm Dis 2017; 4: 124. 3. Revicki DA, Osoba D, Fairclough D, Barofsky I, Berzon R, Leidy N, et al. Recommendations on health-related quality of life research to support labeling and promotional claims in the United States. Qual Life Res 2000; 9: 887-900. 4. Crosby RD, Kolotkin RL, Williams GR. Defining clinically meaningful change in health-related quality of life. J Clin Epidemiol 2003; 56: 395-407. 5. Osoba D, Rodrigues G, Myles J, Zee B, Pater J. Interpreting the significance of changes in health-related quality-of-life scores. J Clin Oncol 1998; 16: 139-144. 6. Jaeschke R, Singer J, Guyatt GH. Measurement of health status: ascertaining the minimal clinically important difference. Control Clin Trials 1989; 10: 407-415. 7. Gatchel RJ, Lurie JD, Mayer TG. Minimal clinically important difference. Spine 2010; 35: 1739-1743. 8. Ali F, Cueva A, Vyas J, Atwan A, Salek M, Finlay A, et al. A systematic review of the use of quality‐of‐life instruments in randomized controlled trials for psoriasis. Br J Dermatol 2017; 176: 577-593. 9. Basra MKA, Salek MS, Camilleri L, Sturkey R, Finlay AY. Determining the minimal clinically important difference and responsiveness of the Dermatology Life Quality Index (DLQI): further data. Dermatology 2015; 230: 27-33. 10. Hongbo Y, Thomas CL, Harrison MA, Salek MS, Finlay AY. Translating the science of quality of life into practice: What do dermatology Life Quality Index Scores Mean? J Invest Dermatol 2005; 125: 659-664.  Figure 1 Mean DLQI score change in 100 clinical trials for psoriasis (8), showing those interventions that reached 1 MCID and 2 MCID score change.     InterventionYinxieling formula at 8 weeksXP-828L (Dermylex) 400 mg at 8 weeksVoclosporin 0.4 mg/kg at 12 weeksVoclosporin 0.3 mg/kg at 12 weeksVoclosporin 0.2 mg/kg at 12 weeksVoclosporin (ISA247) 1.5 mg/kg at 12 weeksVoclosporin (ISA247) 0.5 mg/kg at 12 weeksUstekinumab 90 mg at 24 weeksUstekinumab 90 mg at 12 weeksUstekinumab 45 mg at 24 weeksUstekinumab 45 mg at 12 weeksUstekinumab 45-90 mg with immediate methotrexate withdrawal at 16 weeksTriamcinolone Acetonide 0.1% at 8 weeksTofacitinib 5 mg at 12 weeksTofacitinib 2 mg at 12 weeksTofacitinib 15 mg at 12 weeksSulphurous Mineral Waters Spray at 2 weeksSecukinumab 300 mg at 12 weeksSecukinumab 150 mg at 12 weeksPUVAsol 0.6 mg/kg at 12 weeksPUVAsol 0.6 mg/kg & Isotretinoin 0.5 mg/kg at 12 weeksPlacebo + nUVB at 24 weeks (compared with Methotrexate + nUVB)Mometasone furoate 0.1% at 1 weekMometasone furoate 0.1% + salicylic acid 5% at 1 weekMindfulness-based cognitive therapy at 8 weeksMethotrexate 7.5 mg at 16 weeksMethotrexate 7.5 mg at 12 weeksMethotrexate 15 mg at 16 weeksMethotrexate 15 mg + nUVB at 24 weeksMethotrexate + Folic Acid 5 mg at 12 weeksMethotrexate (without Folic Acid) at 12 weeksLow energy diet at 16 weeksLow Dose Cytokines at 12 weeksLiraglutide 1.8 mg at 8 weeksLeflunomide 20 mg at 24 weeksLCD Solution 15% at 12 weeksIxekizumab 75 mg at 8 weeksIxekizumab 25 mg at 8 weeksIxekizumab 150 mg at 8 weeksItolizumab 1.6 mg/kg at 12 weeksInterdisciplinary dermatological and psychiatric care for psoriasis at 24 weeksInfliximab 5 mg/kg at 50 weeksInfliximab 5 mg/kg at 24 weeksInfliximab 5 mg/kg at 16 weeksInfliximab 5 mg/kg at 14 weeksInfliximab 5 mg/kg at 10 weeksInfliximab 5 mg/kg at 100 weeksInfliximab 3 mg/kg at 50 weeksInfliximab 3 mg/kg at 10 weeksEtanercept 50 mg at 54 weeksEtanercept 50 mg at 24 weeksEtanercept 50 mg at 12 weeksEtanercept 50 mg + nUVB at 12 weeks (Patients who did not achieve PASI 90 after 12 weeks of Etanercept)Etanercept 25 mg at 54 weeksEtanercept 25 mg at 12 weeksEtanercept 25 mg + continued methotrexate treatmentEtanercept 100 mg at 12 weeksEtanercept + tapered methotrexateEnergy-restricted diet at 24 weeksEfalizumab 1 mg/kg at 12 weeksEducational Programme at 12 weeksEducational Nursing Intervention at 6 weeksDermatological care for psoriasis at 24 weeksDAB389IL-2 (5-15 mg/kg) at 4 weeksClobetasol Spray 0.05% at 4 weeksClobetasol Foam 0.05% at 2 weeksClobetasol Cream 0.05% at 2 weeksCiclosporin 3-5 mg/kg at 12 weeksChondroitin sulphate 800 mg at 12 weeksCertolizumab 400 mg at 24 weeksCertolizumab 400 mg at 12 weeksCertolizumab 200 mg at 24 weeksCertolizumab 200 mg at 12 weeksCalcipotriol betamethasone at 8 weeksCalcipotriol betamethasone at 4 weeksCalcipotriol at 4 weeksCalcipotriol 50 mcg/g at 8 weeksCalcipotriene 0.005% at 12 weeksBrodalumab 70 mg at 12 weeksBrodalumab 280 mg at 12 weeksBrodalumab 210 mg at 12 weeksBrodalumab 140 mg at 12 weeksBriakinumab 200 mg at 12 weeksBriakinumab 100 mg at 40 weeksBetamethasone valerate dressing at 4 weeksBetamethasone at 8 weeksAuricular Therapy + Yinxieling formula at 8 weeksApremilast 30 mg at 16 weeksApremilast 20 mg at 16 weeksApremilast 10 mg at 8 weeksAloe Vera 70% at 8 weeksAlefacept 15 mg at 16 weeksAlefacept 15 mg at 12 weeksAlefacept 10 mg at 12 weeksAdalimumab 80 mg at 24 weeksAdalimumab 40 mg at 24 weeksAdalimumab 40 mg at 16 weeksAdalimumab 40 mg at 12 weeksAdalimumab 40 mg + vehicle at 16 weeksAdalimumab 40 mg + calcipotriol betamethasone at 16 weeksChange in DLQI score from baseline7.06.05.04.03.02.01.0 .0-1.0-2.0-3.0-4.0-5.0-6.0-7.0-8.0-9.0-10.0-11.0-12.0-13.0-14.0-15.0 y2MCID1 MCID

Two minimal clinically important difference (2MCID): A new twist on an old concept

Two Minimal Clinically Important Difference (2MCID) : A New Twist on an Old Concept

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