# Presentation: 429701

## OutcomesMulti-systemic Impact:Fibromyalgia

**George A Wells**
**Department of Epidemiology and Community Medicine**
**University of Ottawa**

## Fibromyalgia

**chronic musculoskeletal disorder characterized by widespread pain, exquisite tenderness at specific anatomic sites and other clinical manifestations such as fatigue, sleep disturbance and irritable bowel syndrome ****(Bradley and Alarcon)**
**ACR 1990 criteria for classifying patients with fibromyalgia:**
**widespread pain for at least 3 months (pain in left and right sides of body; pain above and below waist; and axial skeletal pain)**
**tenderness in at least 11 of 18 ‘tender points’**

## Fibromyalgia ...

**Controversy: **
**medicalization of unrelated symptoms**
**syndrome (occurring with other diseases)**
**defined disorder**
**Controversy:**
**What are the most appropriate outcome measures?**

## Outcome Measures

**Types of outcome measures (Fibromyalgia)**
**Choosing outcomes**
**Development and selection of outcomes**
**Overall response criteria**
**Minimal clinically important difference**
**Low disease activity state**

## Outcome Measures

**Types of outcome measures (Fibromyalgia)**
**Choosing outcomes**
**Development and selection of outcomes**
**Overall response criteria**
**Minimal clinically important difference**
**Low disease activity state**

## Types of Outcome Measures(Fibromyalgia) 

**	****Karjalainen K, et al**
**	****Multidisciplinary rehabilitation for fibromyalgia and musculoskeletal pain in working age adults**
**	****Cochrane Collaboration Review 2003**
**	****Busch A, et al**
**	****Exercise for treating fibromyalgia syndrome**
**	****Cochrane Collaboration Review 2002**
**	****Rossy LA, et al****	**
**	****A meta-analysis of fibromyalgia treatment interventions**
**	****Ann Behav Med. 1999**** **

## Types of Outcome Measures ...

**Constructs:**
**Pain**
**Tender points**
**Physical function**
**Global well being or perceived improvement**
**Self efficacy**
**Fatigue and sleep**
**Psychological function**
**Quality of life**

## Types of Outcome Measures ...

_**Pain**_
**visual analogue scale**
**ordinal scale**
**pain drawings**
**Regional Pain Scale (RPS)**
**	****(Wolfe, J Rheumatol 2003)**

## Types of Outcome Measures ...

_**Tender points**_
**pain threshold of tender points using dolorimetry**
**tenderness to thumb pressure**

## Types of Outcome Measures ...

_**Physical function**_
**Self-reported physical function **
**FIQ Physical Impairment subscale**
**FHAQ**
**Musculoskeletal performance**
**grip strength**
**hip and knee extension strength**
**sit and reach test**
**Cardiorespiratory fitness**
**submaximal or maximal treadmill or cycle ergometer tests**
**6 minute walk**

## Types of Outcome Measures ...

_**Global well being or perceived improvement**_
**physician rated change**
**FIQ total score**

## Types of Outcome Measures ...

_**Self efficacy**_
**Arthritis Self-efficacy Questionnaire**

## Types of Outcome Measures ...

_**Fatigue and sleep**_
**FIQ fatigue subscale**
**sleep VAS**

## Types of Outcome Measures ...

_**Psychological function**_
**FIQ subscales for depression and anxiety**

## Types of Outcome Measures ...

_**Quality of life / Generic Functional Status**_
**Short Form 36 (SF36)**
**Sickness Impact Profile (SIP)**
**Health Assessment Questionnaire (HAQ)**

## Fibromyalgia Impact Questionnaire (FIQ)

**brief 10-item self-administered instrument**
**measures**
**physical functioning**
**work status**
**depression**
**anxiety**
**sleep**
**pain**
**stiffness**
**fatigue**
**well-being**
**	****(Burckhardt, Clark, Bennett, J Rheumatol 1991)**

## 
Were you able to:
	a. Do shopping			
	b. Do laundry with a washer and dryer	
	c. Prepare meals
	d. Wash dishes/cooking utensils by hand
	e. Vacuum a rug
	f. Make beds
	g. Walk several blocks
	h. Visit friends/relatives
	I. Do yard work
	j. Drive a car

[0 Always; 1 Most times; 2 Occasionally; 3 Never] 

**Were you able to:**
**	****a. Do shopping****	****	****	**
**	****b. Do laundry with a washer and dryer****	**
**	****c. Prepare meals**
**	****d. Wash dishes/cooking utensils by hand**
**	****e. Vacuum a rug**
**	****f. Make beds**
**	****g. Walk several blocks**
**	****h. Visit friends/relatives**
**	****I. Do yard work**
**	****j. Drive a car**
**[0 Always; 1 Most times; 2 Occasionally; 3 Never] **

## 
Of the days in the past week, how many days did you feel good?
		1   2   3   4   5   6   7

How many days in the past week did you miss work because of your fibromyalgia?	      1   2   3   4   5

When you did go to work, how much did pain or other symptoms of your fibromyalgia interfere with your ability to do your job?
How bad has your pain been?
How tired have you been?
How have you felt when you got up in the morning?
How bad has your stiffness been?
How tense, nervous or anxious have you felt?
How depressed or blue have you been?

[Questions 4 – 10 assessed using a VAS]

**Of the days in the past week, how many days did you feel good?**
**	****	****1   2   3   4   5   6   7**
**How many days in the past week did you miss work because of your fibromyalgia?****	****      1   2   3   4   5**
**When you did go to work, how much did pain or other symptoms of your fibromyalgia interfere with your ability to do your job?**
**How bad has your pain been?**
**How tired have you been?**
**How have you felt when you got up in the morning?**
**How bad has your stiffness been?**
**How tense, nervous or anxious have you felt?**
**How depressed or blue have you been?**
**[Questions 4 – 10 assessed using a VAS****]**

## Fibromyalgia Health Assessment Questionnaire (FHAQ)

**Are you able to (over the past week):**
**	****a. bending****	****	****	**
**	****b. dressing****	**
**	****c. wash body**
**	****d. getting in and out of car**
**	****e. vacuum**
**	****f.  stand up from chair**
**	****g. reach overhead**
**	****h. run errands**
**[0 Without any difficulty; 1 With some difficulty;**
** ****2 With much difficulty; 3 Unable to do]**
**(Wolfe et al, J Rheumatol, 2000)**

## Outcome Measures

**Types of outcome measures (Fibromyalgia)**
**Choosing outcomes**
**Development and selection of outcomes**
**Overall response criteria**
**Minimal clinically important difference**
**Low disease activity state**

## Choosing Outcomes

**objective measurements (validated and accepted to represent appropriate efficacy criteria)**
**reduced or reversed disease progression**
**improved quality of life**
**reduced mortality**
**clinical global impression (physician, patient)**
**improved symptomatology of patient**
**biochemical measures (assessing underlying disease state)**

## Patients desire the following...

**1) to live as long as possible****	****       ****	****[death]****	**
**2) to be normally functioning****	****       ****	****[disability]**
**3) to be free of pain, psychological, **
**	****physical, social and other**
**	****symptoms****	****	****	****	****[discomfort]**
**4) to be free of iatrogenic**
**	****problems from treatments****	****[drug s/e]**
**5) to remain solvent****	****	****	****[destitution]**

## Identifying the best outcomes ...

**influence physicians’ decision**
**combination of outcomes that’s most practical and useful**
**hard measurement**
**change in endpoint that would be clinically significant**

## Identifying the best outcomes ...	influence physicians’ decision

**	****Outcome measurement procedures in routine rheumatology outpatient practice in Canada / Australia**
**	****‘****How often do you serially use the following assessment techniques for longitudinally monitoring the efficacy of antirheumatic drug therapy in your adult fibromyalgia outpatient practice?’**

## Identifying the best outcomes ...	 influence physicians’ decision

**	****	****     ****Never     Occasionally     Usually      Always****   **
_***Canada***_
**Quality of sleep****	****     11%****	**** 11%****	****        28%****	****   50%**
**Fatigue****	****	****     13%****	**** 13%****	****        29%****	****   45%  **
**No. tender points****	****     17%****	**** 15%****	****        29%****	****   39%****	**** **
**Skinfold tenderness   47%****	**** 25%****	****        19%****	****     9%**
_***Australia***_
**Quality of sleep****	****     18%****	****   8%****	****        42%****	****   32%**
**Fatigue****	****	****     21%****	**** 14%****	****        43%****	****   23% **
**No. tender points****	****     38%****	**** 22%****	****        30%****	****   10%**
**(Bellamy J Rheumatol 1998, 1999)**

## Outcome Measures

**Types of outcome measures (Fibromyalgia)**
**Choosing outcomes**
**Development and selection of outcomes**
**Overall response criteria**
**Minimal clinically important difference**
**Low disease activity state**

## Criteria for Development and Selection of Outcomes

**Comprehensive**** (content validity)**
**	****	****- includes appropriate components of health**
**Credibility**** (face validity)**
**	****	****- appears sensible and interpretable**
**Accuracy**** (criterion validity)**
**	****	****- consistently reflects true clinical status of patients**
**Sensitivity to change**** (discriminant validity)**
**	****	****- detects smallest clinically important difference**
**Biological sense**** (construct validity)**
**	****	****- matches hypothesized expectations when compared ****	****  with other indirect measures**

## Health Measurement

**Reliability**
**Validity**
**Sensitivity to Change**

## Reliability

**Reflection of the amount of error, both random (mechanical inaccuracy, measurement mistakes) and systematic, inherent to any measurement**
**Determines how reproducible is the scale under different conditions**

## Reliability

**The reliability coefficient expresses the proportion of the total variance in the measurements (denominator), which is due to true differences between subjects (numerator)**

## Reliability

**Reproducibility**
**Test-retest reliability**
**Intra-rater reliability**
**Inter-rater reliability**
**Internal consistency**** ****of a scale (correlation among items composing an instrument)**

## Reliability: Reproducibility

**Intra-class correlation (ICC)**
**	****(based on ANOVA)**
**Pearson’s r**
**Kendall’s index of concordance**
**Kappa coefficient**
**Bland and Altman**

## Reliability: Reproducibility

**Other considerations:**
**Observations as fixed factor**
**test always done by same observers**
**same items completed by all**
**Observations as random factor**
**observer varies**

## Reliability: Reproducibility

**Other considerations (cont’d):**
**Observer nested within subject**
**several subjects evaluated by several observers**
**no observer common to more than one subjects**
**One-way ANOVA**
**subject as  grouping factor**
**multiple observations within each cell as ‘within-subject’ factor **

## Reliability: Reproducibility

**Other considerations (cont’d):**
**multiple observations k**
**multiple items on questionnaire**
**multiple observers**
**repeated use of an instrument**

## Reliability: Internal Consistency

**Represents the average of the correlations among all items in the measure**
**All the items should be ‘tapping’ different aspects of the same attribute**
**items should be moderately correlate with each other**
**each should correlate with the total scale score**

## Reliability: Internal Consistency

**Item-total correlation**
**checks homogeneity of scale**
**correlation of individual item with scale score omitting that item**
**Pearson correlation (working rule: >0.2)**
**Split-half reliability**
**splits scale in half, each half is correlated with the other**
**Spearman-Brown**
**Kuder-Richardson 20**
**scales with dichotomous items**
**Cronbach’s aplha**
**scales with ordinal items**
**should be >0.70 but <0.90 (item redundancy)**

## Reliability: Improving IT

**Reduce error variance**
**observer training**
**elimination of extreme observers**
**improve scale design**
**Increase true variance**
**introduce items resulting in performance nearer middle of scale**
**modify descriptors on the scale**
**Increase number of items**
**as long as items not perfectly correlated**

## Validity

**Determine the degree of confidence we can place on inferences made based on the scores from the scale**

## Validity

**Content**
**cover all domains of interest**
**sufficient number of items**
**inferred from experts**
**Criterion**
**test against a ‘gold’ standard**
**Concurrent**
**gold standard and the new instrument are applied at the same time**
**  **
**Predictive**
**gold standard is applied in the future**

## Validity

**Construct**
**if no gold standard exists**
**based on conceptual definition of construct to be measured**
**defines hypotheses of what should or should not correlate**
**Correlational**
**	****Convergent**
**instrument tested should correlate with other methods that measure same concept**
** **
**Divergent**
**instrument should not correlate with other methods that measure different themes**

## Validity

**Construct**** ****(cont’d)**
**Factorial analysis**
**examines how items measure one or more common themes**
**analysis forms the questions into groups or factors that appear to measure common themes with each factor distinct from the others**
**Multi-trait multi-method analysis**
**method for considering convergent and discriminant validity simultaneously**

## Validity

**Evaluation using:**
**Correlations**
**Receiver operator characteristic (ROC) curves**
**2x2 tables (sensitivity and specificity)**

## Sensitivity to Change

**	****Ability of an instrument to detect small but clinically important clinical**
**	****Particularly important where subjective reports of health status is one of the primary outcomes of the trial**

## Sensitivity to Change

**t-test**** **
**compares means at baseline and follow-up**
**Effect-size**** **
**relates changes in mean score (from baseline to follow-up) to the standard deviation of baseline score**
**ROC Curve**
**Evaluate how a given change score can discriminate between patients who improve from those who do not**

## FIQ

**(Burckhardt et al, J Rheumatol 1991) **
**	****[evidence of reliability and validity]**
**Reliability:**
**	****test-retest reliability correlations for FIQ items ranged from 0.56 to 0.95**
**Content validity:**
**	****assessed by calculating percent missing data: 11% washing by hand item,  20% yard work item, 38% job working items**
**Construct validity:**
**	****(1) correlational analysis comparing FIQ items/scales to corresponding ones of  AIMS: physical functioning item 0.67; pain 0.69; depression 0.73; anxiety 0.76**
**	****(2) correlational analysis comparing FIQ items with measures of symptom severity: AIMS impact analog (0.17 to 0.48), AIMS syndrome activity (0.28 to 0.83) and tender points (0.14 to 0.74)**
**	****(3) factor analysis to determine if items of physical functioning loaded on single factor (eg. 10 items of FIQ loaded on same factor)**

## FIQ ...

**(Dunkl et al, J Rheumatol 2000)**
**	****[responsive to perceived clinical improvement]**
**Sensitivity to Change:**
**	**
**	****	****Patient Global**
**	****	****Improvement****	****	****FIQ mean (sd)**
**	****	****Improved****	****	****34.11 (17.48)**
**	****	****Unchanged****	****	****46.92 (15.44)**
**	****	****Worsened****	****	****57.92 (15.23)**
**(Wolfe et al, J Rheumatol 2000)**
**	****[FIQ systematically underestimates functional impairment by its handling of activities not usually performed]**

## 6 Minute Walk (6-MWT)

**(Pankoff et al, J Rheumatol 2000)**
**	****[not a valid predictor of cardiorespiratory fitness; sensitive to change; related to FIQ score]**
**Sensitivity to Change:**
**	**
**	****	****	****	**** ****Before ****	**** ****	**** After**
**	****	****	****	****Exercise****	****Exercise****	****p-value**
**	****6-MWT, m****	****	****487  (75)****	****565 (58)****	****	****<0.001**
**	****PVO2, ml/kg/min****	****19.6 (4.5)****	****21.4 (4.8)****	****  0.001**
**	****FIQ Total****	****	****47.9 (12.1)****	****38.0 (12.9)****	****  0.012**
**	****FIQ Phys****	****	****  3.1 (1.7)****	****  2.3 (1.9)****	****  0.0.62**
**Validity:**
**Correlation of change scores:****	****6-MWT, PVO2 (r=0.081)**
**	****	****	****	****	****6-MWT, FIQ Total (r=0.592)**
**	****	****	****	****	****6-MWT, FIQ Phys (r=0.245)  **

## Generic versus Specific

***The use of generic and specific quality of life measures in fibromyalgia patients ******(Wolfe et al, J Rheumatol 2000)***
**Instruments**
**Generic: SF-36, HAQ, MHAQ, IHAQ**
**Specific: FIQ, FHAQ**
**Methods**
**FM patient (**_**FIQ**_**: Boston 1928, San Antonio 233, US multicenter 333, Beer Sheva 100; **_**HAQ**_** National Data Bank for Rheumatic Diseases 1438; **_**SF-36**_** Wichita 760) **
**Rasch analysis (based on item response theory)**
**Results**
**no functional assessment questionnaire works well**
**FIQ underestimates functional impairment by handling activities not usually performed**
**developed FHAQ (subset of HAQ) with appropriate metric properties**** ****and should function well; need to assess sensitivity to change**

## Outcome Measures

**Types of outcome measures (Fibromyalgia)**
**Choosing outcomes**
**Development and selection of outcomes**
**Overall response criteria**
**Minimal clinically important difference**
**Low disease activity state**

## Core set of outcome measures
reliable, valid, sensitive to change
consider in combination (patient profiles)

Conduct survey of clinicians  providing information on randomly selected patients from clinical trials near thresholds of improvement
for outcome measures, data at baseline, end of study and percentage change provided for each patient
surveyed clinicians indicated whether each patient improved
analysis focused on patients characterized improved by ‘vast’ majority of surveyed clinicians

**reliable, valid, sensitive to change**
**consider in combination (patient profiles)**
**Conduct survey of clinicians  providing information on randomly selected patients from clinical trials near thresholds of improvement**
**for outcome measures, data at baseline, end of study and percentage change provided for each patient**
**surveyed clinicians indicated whether each patient improved**
**analysis focused on patients characterized improved by ‘vast’ majority of surveyed clinicians**

_**Improvement Criteria**_

## 
Statistical analysis of clinical trial data for selecting definition of improvement 
data sets assembled of appropriate placebo controlled trials with ‘very’ efficacious interventions and included outcome measures
improvement criteria selected that best discriminates an efficacious intervention from placebo

Evaluate definition of improvement in large comparative trials

Improvement definition selected based on ease of use and credibility
with experienced trialists ranking face validity

**Statistical analysis of clinical trial data for selecting definition of improvement**** **
**data sets assembled of appropriate placebo controlled trials with ‘very’ efficacious interventions and included outcome measures**
**improvement criteria selected that best discriminates an efficacious intervention from placebo**
**Evaluate definition of improvement in large comparative trials**
**Improvement definition selected based on ease of use and credibility**
**with experienced trialists ranking face validity**

_**Improvement Criteria**_** ...**

## Preliminary Criteria for Response to Treatment in Fibromyalgia

**	****	****	****	****(Simms et al, J Rheumatol 1991)**
**Methods:**
**clinical trial of amitriptyline vs placebo for treating fibromyalgia (amitriptyline was found to be significantly more efficacious)**
**proxy response: treatment with effective medication (amitripyline)**
**outcome measures available: physician global, patient global, pain, fatigue, sleep, tender point score**
**used logistic regression(s) to determine predictors of response**
**considered combinations of outcome measures and plotted ROC curves to determine criteria with optimal sensitivity / specificity**
**applied criteria to unreported trial (cyclobenzaprine vs placebo)**

## Preliminary Criteria for Response to Treatment in Fibromyalgia ...

**Criteria:**
**	****(1) physician global assessment score <= 4**
**	****	****	****(0 = extremely well, 10 = extremely poorly)**
**	****(2) patient sleep <= 6**
**	****	****	****(0 = sleeping extremely well, 10 = sleeping ****	****	****	****	****extremely poorly)**
**	****(3) tender point score <= 14**
**	****	****	****(maximum possible 20)**
**Future Work:**
**	****as sensitive and clinically relevant outcomes are developed, can apply this methodology to refine criteria **

## Outcome Measures

**Types of outcome measures (Fibromyalgia)**
**Choosing outcomes**
**Development and selection of outcomes**
**Overall response criteria**
**Minimal clinically important difference**
**Low disease activity state**

## Two Steps

**Studies of Responsiveness**
**A classification system (Beaton, Bombardier et al, J Rheumatol 2003)**
**Minimal Clinically Important Differences**
**A review of methods (Wells, Tugwell et al, J Rheumatol 2003)**

## clinical studies are often aimed at discriminating between groups of interest

differences are often change over time (eg. response to therapy)
‘change’ (within-patient change over time)
‘differences’ (between patients)
‘hybrid’ (between group differences of within-patient change)

studies of responsiveness evaluate the ability of an outcome measure to accurately detect change when it has occurred

**differences are often change over time (eg. response to therapy)**
**‘****change’ (within-patient change over time)**
**‘****differences’ (between patients)**
**‘****hybrid’ (between group differences of within-patient change)**
**studies of responsiveness evaluate the ability of an outcome measure to accurately detect change when it has occurred**

_**Studies of Responsiveness**_

## Construct of change in studies of responsiveness

**Each study defines the change/difference it is examining**
**Defined by three key features (axes**):
**Setting: individual versus group-level?***** ***
**Which data is being compared?**
**What kind of change is being quantified?**

## Key features addressed in defining change/difference

## Key features addressed in defining change/difference

## Key features addressed in defining change/difference

**Minimum potentially detectable**

**Observed in those estimated to have an *****important difference*****/ change**

**Observed in those estimated to differ/ to have  changed**

**Observed in population**

**Minimum actually detectable beyond error**

## 

These 3 features are mutually independent and fit together into a ‘cube’ with each cell describing the ‘construct of change’  built into the study of responsiveness

The cube becomes a classification system, classifying the nature of discrimination (either differences of changes) built into studies of responsiveness

**These 3 features are mutually independent and fit together into a ‘cube’ with each cell describing the ‘construct of change’  built into the study of responsiveness**
**The cube becomes a classification system, classifying the nature of discrimination (either differences of changes) built into studies of responsiveness**

## Classification of  discrimination (differences and changes)  in studies

_**Classification of  discrimination (differences and changes)  in studies**_

**3. both: differences**
**between**
**changes within**

**2. changes within**

**1. differences between**

**Which****?**

***Setting: Who***
*** ******is the focus?***

**What kind of change/difference**

**Minimum potentially detectable**

**Observed in those estimated to have an *****important difference*****/ change**

**Observed in those estimated to differ/ to have  changed**

**Observed in population**

**Minimum actually detectable beyond error**

***1. - group***

***2. - individual***

***1.                 2.                3.                4.                  5.***

## Summary

- Responsiveness studies look at varying kinds of change/difference
- Some will be helpful in pursuit of MCID
- “Cube” of discrimination helps to sort through the literature
- Point to those articles that might be useful
- Separates out those that will not help

## Two Steps

**Studies of Responsiveness**
**A classification system (Beaton, Bombardier et al, J Rheumatol 2003)**
**Minimal Clinically Important Differences**
**A review of methods (Wells, Tugwell et al, J Rheumatol 2003)**

## MCID 
a MCID can be considered as the smallest change or difference in an outcome measure that is perceived as beneficial and would lead to a change in the patient’s management, assuming an absence of excessive side effects and costs

Purpose
to consider and classify the different methods that have been used in detecting important changes or differences for the purposes of developing the MCID or an outcome measure

Method
extensive literature search to retrieve all relevant articles related to specific topics on MCID
‘methods section’ of the retrieved articles was reviewed
methodology followed was used to categorize study according to the ‘cube’ classification

- a MCID can be considered as the smallest change or difference in an outcome measure that is perceived as beneficial and would lead to a change in the patient’s management, assuming an absence of excessive side effects and costs
**Purpose**
- to consider and classify the different methods that have been used in detecting important changes or differences for the purposes of developing the MCID or an outcome measure
**Method**
- extensive literature search to retrieve all relevant articles related to specific topics on MCID
- ‘methods section’ of the retrieved articles was reviewed
- methodology followed was used to categorize study according to the ‘cube’ classification

## Methods for Determining Minimal Clinically Important Differences

**1.  Comparison to global rating**
- Patients global ratings
- Clinical assessments
- Change scale; MCID “small” change

**2.  Patient conversation**
- Patients comparative ratings
- Clinical assessments
- Comparative ratings; MCID “small” change

**3.  Consensus Development**
- Clinicians examine statistics
- Compare groups
- MCID : hypothetical RCT

**4. Patient scenario scoring**
- Clinicians suggest change
- Average response
- Assess change using options; MCID chosen option vs initial

**5.  Patient scenario comparison**
- Clinicians contrast scenarios
- Average assessment
- Assess change using option. MCID “small” change

**6. Prognostic rating scale**
- Clinicians describe changes
- ROC analysis
- Prognostic rating

**7. Data driven**
-  SEM
-  Longitudinal change score
-  SEM proxy for MCID

**8.  Improvement criteria**
- Survey clinicians
- Patients near improvement threshold
- Improved if indicated by “vast” majority; RCT data

**9. Achieving treatment goals**
- Patients followed
- Best improvement cut-point
- Treatment goals achieved; ROC analysis

**Methods for Determining Minimal Clinically Important Differences**

- 3. both: differences between changes within

- 2. changes within

- 1. differences between

**Which?**

***Setting***

**Minimum potentially detectable**

**Observed in those estimated to differ/ to have  changed**

**Observed in population**

**Minimum actually detectable beyond error**

**Type of Change/Difference**

**Individual**

**Group**

**Observed in those estimated to have an *****important difference*****/ change**

**Patient Perspective**

**Clinical Perspective**

**Clinician Perspective**

**Discerning important improvement**

## Methods for Determining Minimal Clinically Important Differences

**Methods for Determining Minimal Clinically Important Differences**

- 3. both: differences between changes within

- 2. changes within

- 1. differences between

**Which?**

***Setting***

**Minimum potentially detectable**

**Observed in those estimated to differ/ to have  changed**

**Observed in population**

**Minimum actually detectable beyond error**

**Type of Change/Difference**

**Individual**

**Group**

**Observed in those estimated to have an *****important difference*****/ change**

**Patient Perspective**

**Clinical Perspective**

**Clinician Perspective**

**Discerning important improvement**

## Summary

**most methods consider important change form the viewpoint of a group of patients**
**contrast of groups considered from all perspectives**
**for setting, only a few methods considered within individuals**
**need more development of methods that focus on individuals**

## Outcome Measures

**Types of outcome measures (Fibromyalgia)**
**Choosing outcomes**
**Development and selection of outcomes**
**Overall response criteria**
**Minimal clinically important difference**
**Low disease activity state**

## Low Disease Activity State Workshop

**Objectives of workshop:**
- 	**to meet the many challenges that exist in determining a low disease activity state by reviewing the concepts and terminologies associated with a low disease activity state and determining the processes for developing an operational definition of low disease activity state**
- 	**working definition for low disease activity state:**
- 	**“****a state that is deemed a useful treatment target by patients and physicians”**

## Research Agenda Overview:

**Review and obtain consensus on the specific outcomes that should be considered in the definition of low disease activity state for RA**
**Design and conduct an assessment of evaluating the outcomes sleep and energy /fatigue using valid and reliability measuring instruments**
**Design and conduct an opinion-based and observation-based approach for the determining a low disease activity state for RA**
**Design and conduct a study to compare the attributes of a weighted, unweighted and tree approach for formulating a low disease activity state for RA**

## Next Steps

**To come to a concrete definition:**
**opinions of physicians and patients will be collected**
**based on these opinions, candidate definitions will be composed and tested in datasets**
**results of this work will be collated and circulated prior to the workshop**
**at the workshop, discussions will continue in plenary and small group sessions to resolve remaining issues, and come up with one or a limited number of ‘top’ candidates that can then be validated**

## George A. Wells

**George A. Wells**
**Department of Epidemiology**
**and Community Medicine**
**University of Ottawa**
**Ottawa, Ontario, Canada**
**e-mail:   gwells.uottawa.ca**