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How Glaucoma Patients Assess Different
      Aspects of Their Treatment?
 An Elicitation of Patients’ Preferences by
    Analytic Hierarchy Process (AHP)

Dintsios CM / Scheibler FF / Janssen I / Gerber A / Finger
                            R

              HTAi, Bilbao, June 25th 2012
Weighting treatment aspects

         Rationale: Why calculate weights?
 Patients weight different treatment aspects according to
  their preferences  Patients’ preferences
 These aspects may serve as patient-relevant measures
  (endpoints) in HTA  Patients’ involvement
 By weighting treatment aspects prioritization is based on
  patients’ views  Legitimating
 In benefit assessments or cost-effectiveness analyses the
  derived weights can be used for the aggregation of
  multiple (composite) endpoints  Endpoint aggregation
…
Page 2            © Dintsios | HTAi | Bilbao, June 25 th2012 | Glaucoma patients’
AHP

                 Rationale: Why AHP?

Patient preferences as a basis for weighting treatment aspects


      elicit preferences via AHP
      AHP is one method – others are available, e.g.
      Conjoint Ananlysis




 Page 3           © Dintsios | HTAi | Bilbao, June 25 th2012 | Glaucoma patients’
Objective of the AHP



  To weigh the different aspects of glaucoma
   treatment by eliciting the preferences of patients
   with the AHP-procedure.

  I.e. to estimate the „relative importance“ of
   treatment aspects, especially importance to
   patients



Page 4         © Dintsios | HTAi | Bilbao, June 25 th2012 | Glaucoma patients’
Background


 The mathematician Thomas L. SAATY developed the AHP
  procedure in the early 1970th as a technique to solve
  multicriteria decision problems

 How the procedure works:
    Decision issues are structured hierarchically into
     different levels of criteria / alternatives.




Page 5            © Dintsios | HTAi | Bilbao, June 25 th2012 | Glaucoma patients’
Hierarchical Structure of the AHP

                                                      Decision Problem
                                                    (which car do I want?)




                                                 Criterium22
                                                   Criterion
                      Criterium 1
                        Criterion 1
                                                (e.g. gasoline                ...                  Criteriumnn
                                                                                                    Criterion
                     (e.g. colour)
                                                consumption)



         Criterium 1.1                ...




              ...




                     Alternative 1              Alternative 2
                                                                              ...                 Alternative n
                    (Peugeot 206)                   (Golf)




Page 6                                      © Dintsios | HTAi | Bilbao, June 25 th2012 | Glaucoma patients’
How the AHP works


  Pairwise comparisons of criteria are used to elicit the
   relative importance of one criterion in comparison to
   the others

  Mathematical procedure: based on matrices of
   pairwise comparisons weights are calculated for
   each criterion with the help of the „Eigenvector“-
   method




Page 7          © Dintsios | HTAi | Bilbao, June 25 th2012 | Glaucoma patients’
AHP scale used in pairwise comparisons

   How much more important is criterion A in
    comparison to criterion B?



         9   7   5       3           1           3           5           7             9



         A                   Equal importance                                      B
                         1    -    equally important
                         3    -    slightly more important
                         5    -    more important
                         7    -    much more important
                         9    -    extremely more important




Page 8               © Dintsios | HTAi | Bilbao, June 25 th2012 | Glaucoma patients’
AHP Matrix


 AHP matrix of pairwise comparisons


                  A                 B                C

         A        1                 1/5               2


         B        5                    1               6


         C        1/2                 1/6              1




Page 9            © Dintsios | HTAi | Bilbao, June 25 th2012 | Glaucoma patients’
Mathematical conditions on the AHP structure

 1) Completeness of criteria  a complete set of criteria
    should be assessed

 2) Independence of preference information  at the
    different levels of hierarchy

 3) Independence of criteria  should be disjunct, exclude
    each other

 4) Scale should be a relative scale  preferences
    measured on a common relative scale



Page 10           © Dintsios | HTAi | Bilbao, June 25 th2012 | Glaucoma patients’
Prerequisites


 The preferences of individuals should correspond to the following
 prerequisites

 1) Reciprocity
         if A is 3 times more important than B, then B is 1/3 as important
          as A
 2) Transitivity
         if A >B and B>C then A>C
 3) Consistency
         resulting from reciprocity and transitivity




Page 11                 © Dintsios | HTAi | Bilbao, June 25 th2012 | Glaucoma patients’
Calculation of the right “Eigenvector” (I)


Pairwise comparison matrix A; relative weights w1, w2 und w3
of the compared elements are known




Multiply matrix A with the vector W of the weights:
                                                                                    3 x w1
                                                                                    3 x w2
                                                                                    3 x w3




 This equates to the multiplication of the respective weight
with the number of the compared elements n

 Page 12          © Dintsios | HTAi | Bilbao, June 25 th2012 | Glaucoma patients’
Calculation of the right “Eigenvector” (II)

This relation is described by the following equation:
              A x W = n x W
with A = pairwise comparison matrix,
W = vector of the weights, n = compared elements

In Matrix Algebra: W = right „Eigenvector“
                   n = Eigen-value of matrix A

 In reality W is unknown and has to be approximated by a
regression analysis approach



 Page 13          © Dintsios | HTAi | Bilbao, June 25 th2012 | Glaucoma patients’
Calculation of the right “Eigenvector” (III)

This transforms the equation to:

             A* x W* = λmax x W*

with A* = pairwise comparison matrix, W* = right Eigenvector of
matrix A, λmax = maximal Eigen-value of matrix A*

Basic assumption of AHP: the calculated right Eigenvector of
matrix A equates approximately the vector of the relative
weights



 Page 14          © Dintsios | HTAi | Bilbao, June 25 th2012 | Glaucoma patients’
Inconsistency

 Is measured by the so called Consistency Ratio (CR)
 Is checking for the „logic“ of the particular pairwise
  comparison, (i. e. how consistent is the respective
  pairwise comparison with regard to all the other
  pairwise comparisons)
 According to SAATY a CR ≤ 0,1 is accepted and
  allows for the conclusion that the weights are
  derived on a consistent basis




 Page 15         © Dintsios | HTAi | Bilbao, June 25 th2012 | Glaucoma patients’
Inconsistent judgments




                 A>B>C>A



Page 16    © Dintsios | HTAi | Bilbao, June 25 th2012 | Glaucoma patients’
Patient sample


n     N = 7 Pretest => Language abilities, Cognition, Proxies
n     N = 25 Patients
n     Setting: Ophthalmology ambulance at University of Bonn
n     Glaucoma patients: different manifestations and severities
n     AHP-Questionnaire
n     Elicitation of utilities with EQ5D – VAS
n     Stratification according to these utilities




Page 17                 © Dintsios | HTAi | Bilbao, June 25 th2012 | Glaucoma patients’
Patients’ characteristics

 N = 25 Study; 68,3±13,3 years; €€8 •17; first diagnosis 1 – 21 years
 Glaucoma
          Primary chronic wide-angle glaucoma 55%
          Narrow-angle (congestive) glaucoma 9%
          Wide-angle glaucoma with narrow-angle component 9%
          Normal-tension glaucoma 9%
          Suspected glaucoma 18%
 visual acuity bad eye 0,59 ± 0,33
 Tensio RE 17,2 ± 6,2; Tensio LE 18,1 ± 4,7
 Glaucoma management +/- 82%/18%




 Page 18               © Dintsios | HTAi | Bilbao, June 25 th2012 | Glaucoma patients’
Assessed aspects


 Reading and seeing detail
 Peripheral vision
 Darkness and glare
 Autonomy subdivided in:
       household chores
       outdoor mobility
 Treatment-related patient’s burden
 Side effects



Page 19          © Dintsios | HTAi | Bilbao, June 25 th2012 | Glaucoma patients’
Example: Questionnaire different side effects




 Page 20        © Dintsios | HTAi | Bilbao, June 25 th2012 | Glaucoma patients’
EQ-5D VAS




  21
Page 21     © Dintsios | HTAi | Bilbao, June 25 th2012 | Glaucoma patients’
Inconsistency = 0.04




                                                                         Inconsistency
                                                                             = 0.00




                                                                                              Inconsistency
                                                                                                  = 0.01
Page 22                          © Dintsios | HTAi | Bilbao, June 25 th2012 | Glaucoma patients’
Results
                                                  weight, mean, sd, CI95%
 Reading and seeing detail 0.229, 0.212 ± 0.123, 0.161 - 0.263
 Peripheral vision                                               0.089, 0.085 ± 0.058, 0.061
    - 0.109
 Darkness and glare                              0.153, 0.165 ± 0.111, 0.119 - 0.211

 Autonomy subdivided in:                         0.394, 0.371 ± 0.145, 0.311 - 0.431

    household chores                             0.239, 0.275 ± 0.258, 0.168 - 0.381

    outdoor mobility                             0.761, 0.725 ± 0.258, 0.619 - 0.832

 Treatment-related burden                        0.047, 0.052 ± 0.050, 0.027 - 0.076

 Side effects                                    0.088, 0.115 ± 0.131, 0.060 - 0.168

 Utilities EQ-5D vs VAS (82.76 ± 22.21 vs. 65.64 ± 19.95, p =
    0.003)
  Page 23           © Dintsios | HTAi | Bilbao, June 25 th2012 | Glaucoma patients’
Stratified population comparison
Autonomy
Reading details
Darkness & Glare
Peripheral vision
Side effects
Treatment burden




  U > 80 (N = 7)
Autonomy
Reading details
Darkness & Glare
Peripheral vision
Side effects
Treatment burden




  U < 65 (N = 11)
Autonomy
Reading details
Darkness & Glare
Peripheral vision
Side effects
Treatment burden



    Page 24          © Dintsios | HTAi | Bilbao, June 25 th2012 | Glaucoma patients’
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How Glaucoma Patients Assess Different Aspects of Their Treatment? An Elicitation of Patients’ Preferences by Analytic Hierarchy Process (AHP)

  • 1. How Glaucoma Patients Assess Different Aspects of Their Treatment? An Elicitation of Patients’ Preferences by Analytic Hierarchy Process (AHP) Dintsios CM / Scheibler FF / Janssen I / Gerber A / Finger R HTAi, Bilbao, June 25th 2012
  • 2. Weighting treatment aspects Rationale: Why calculate weights?  Patients weight different treatment aspects according to their preferences  Patients’ preferences  These aspects may serve as patient-relevant measures (endpoints) in HTA  Patients’ involvement  By weighting treatment aspects prioritization is based on patients’ views  Legitimating  In benefit assessments or cost-effectiveness analyses the derived weights can be used for the aggregation of multiple (composite) endpoints  Endpoint aggregation … Page 2 © Dintsios | HTAi | Bilbao, June 25 th2012 | Glaucoma patients’
  • 3. AHP Rationale: Why AHP? Patient preferences as a basis for weighting treatment aspects  elicit preferences via AHP  AHP is one method – others are available, e.g. Conjoint Ananlysis Page 3 © Dintsios | HTAi | Bilbao, June 25 th2012 | Glaucoma patients’
  • 4. Objective of the AHP  To weigh the different aspects of glaucoma treatment by eliciting the preferences of patients with the AHP-procedure.  I.e. to estimate the „relative importance“ of treatment aspects, especially importance to patients Page 4 © Dintsios | HTAi | Bilbao, June 25 th2012 | Glaucoma patients’
  • 5. Background  The mathematician Thomas L. SAATY developed the AHP procedure in the early 1970th as a technique to solve multicriteria decision problems  How the procedure works:  Decision issues are structured hierarchically into different levels of criteria / alternatives. Page 5 © Dintsios | HTAi | Bilbao, June 25 th2012 | Glaucoma patients’
  • 6. Hierarchical Structure of the AHP Decision Problem (which car do I want?) Criterium22 Criterion Criterium 1 Criterion 1 (e.g. gasoline ... Criteriumnn Criterion (e.g. colour) consumption) Criterium 1.1 ... ... Alternative 1 Alternative 2 ... Alternative n (Peugeot 206) (Golf) Page 6 © Dintsios | HTAi | Bilbao, June 25 th2012 | Glaucoma patients’
  • 7. How the AHP works  Pairwise comparisons of criteria are used to elicit the relative importance of one criterion in comparison to the others  Mathematical procedure: based on matrices of pairwise comparisons weights are calculated for each criterion with the help of the „Eigenvector“- method Page 7 © Dintsios | HTAi | Bilbao, June 25 th2012 | Glaucoma patients’
  • 8. AHP scale used in pairwise comparisons How much more important is criterion A in comparison to criterion B? 9 7 5 3 1 3 5 7 9 A Equal importance B 1 - equally important 3 - slightly more important 5 - more important 7 - much more important 9 - extremely more important Page 8 © Dintsios | HTAi | Bilbao, June 25 th2012 | Glaucoma patients’
  • 9. AHP Matrix AHP matrix of pairwise comparisons A B C A 1 1/5 2 B 5 1 6 C 1/2 1/6 1 Page 9 © Dintsios | HTAi | Bilbao, June 25 th2012 | Glaucoma patients’
  • 10. Mathematical conditions on the AHP structure 1) Completeness of criteria  a complete set of criteria should be assessed 2) Independence of preference information  at the different levels of hierarchy 3) Independence of criteria  should be disjunct, exclude each other 4) Scale should be a relative scale  preferences measured on a common relative scale Page 10 © Dintsios | HTAi | Bilbao, June 25 th2012 | Glaucoma patients’
  • 11. Prerequisites The preferences of individuals should correspond to the following prerequisites 1) Reciprocity  if A is 3 times more important than B, then B is 1/3 as important as A 2) Transitivity  if A >B and B>C then A>C 3) Consistency  resulting from reciprocity and transitivity Page 11 © Dintsios | HTAi | Bilbao, June 25 th2012 | Glaucoma patients’
  • 12. Calculation of the right “Eigenvector” (I) Pairwise comparison matrix A; relative weights w1, w2 und w3 of the compared elements are known Multiply matrix A with the vector W of the weights: 3 x w1 3 x w2 3 x w3  This equates to the multiplication of the respective weight with the number of the compared elements n Page 12 © Dintsios | HTAi | Bilbao, June 25 th2012 | Glaucoma patients’
  • 13. Calculation of the right “Eigenvector” (II) This relation is described by the following equation: A x W = n x W with A = pairwise comparison matrix, W = vector of the weights, n = compared elements In Matrix Algebra: W = right „Eigenvector“ n = Eigen-value of matrix A  In reality W is unknown and has to be approximated by a regression analysis approach Page 13 © Dintsios | HTAi | Bilbao, June 25 th2012 | Glaucoma patients’
  • 14. Calculation of the right “Eigenvector” (III) This transforms the equation to: A* x W* = λmax x W* with A* = pairwise comparison matrix, W* = right Eigenvector of matrix A, λmax = maximal Eigen-value of matrix A* Basic assumption of AHP: the calculated right Eigenvector of matrix A equates approximately the vector of the relative weights Page 14 © Dintsios | HTAi | Bilbao, June 25 th2012 | Glaucoma patients’
  • 15. Inconsistency  Is measured by the so called Consistency Ratio (CR)  Is checking for the „logic“ of the particular pairwise comparison, (i. e. how consistent is the respective pairwise comparison with regard to all the other pairwise comparisons)  According to SAATY a CR ≤ 0,1 is accepted and allows for the conclusion that the weights are derived on a consistent basis Page 15 © Dintsios | HTAi | Bilbao, June 25 th2012 | Glaucoma patients’
  • 16. Inconsistent judgments A>B>C>A Page 16 © Dintsios | HTAi | Bilbao, June 25 th2012 | Glaucoma patients’
  • 17. Patient sample n N = 7 Pretest => Language abilities, Cognition, Proxies n N = 25 Patients n Setting: Ophthalmology ambulance at University of Bonn n Glaucoma patients: different manifestations and severities n AHP-Questionnaire n Elicitation of utilities with EQ5D – VAS n Stratification according to these utilities Page 17 © Dintsios | HTAi | Bilbao, June 25 th2012 | Glaucoma patients’
  • 18. Patients’ characteristics  N = 25 Study; 68,3±13,3 years; €€8 •17; first diagnosis 1 – 21 years  Glaucoma  Primary chronic wide-angle glaucoma 55%  Narrow-angle (congestive) glaucoma 9%  Wide-angle glaucoma with narrow-angle component 9%  Normal-tension glaucoma 9%  Suspected glaucoma 18%  visual acuity bad eye 0,59 ± 0,33  Tensio RE 17,2 ± 6,2; Tensio LE 18,1 ± 4,7  Glaucoma management +/- 82%/18% Page 18 © Dintsios | HTAi | Bilbao, June 25 th2012 | Glaucoma patients’
  • 19. Assessed aspects  Reading and seeing detail  Peripheral vision  Darkness and glare  Autonomy subdivided in:  household chores  outdoor mobility  Treatment-related patient’s burden  Side effects Page 19 © Dintsios | HTAi | Bilbao, June 25 th2012 | Glaucoma patients’
  • 20. Example: Questionnaire different side effects Page 20 © Dintsios | HTAi | Bilbao, June 25 th2012 | Glaucoma patients’
  • 21. EQ-5D VAS 21 Page 21 © Dintsios | HTAi | Bilbao, June 25 th2012 | Glaucoma patients’
  • 22. Inconsistency = 0.04 Inconsistency = 0.00 Inconsistency = 0.01 Page 22 © Dintsios | HTAi | Bilbao, June 25 th2012 | Glaucoma patients’
  • 23. Results weight, mean, sd, CI95%  Reading and seeing detail 0.229, 0.212 ± 0.123, 0.161 - 0.263  Peripheral vision 0.089, 0.085 ± 0.058, 0.061 - 0.109  Darkness and glare 0.153, 0.165 ± 0.111, 0.119 - 0.211  Autonomy subdivided in: 0.394, 0.371 ± 0.145, 0.311 - 0.431  household chores 0.239, 0.275 ± 0.258, 0.168 - 0.381  outdoor mobility 0.761, 0.725 ± 0.258, 0.619 - 0.832  Treatment-related burden 0.047, 0.052 ± 0.050, 0.027 - 0.076  Side effects 0.088, 0.115 ± 0.131, 0.060 - 0.168  Utilities EQ-5D vs VAS (82.76 ± 22.21 vs. 65.64 ± 19.95, p = 0.003) Page 23 © Dintsios | HTAi | Bilbao, June 25 th2012 | Glaucoma patients’
  • 24. Stratified population comparison Autonomy Reading details Darkness & Glare Peripheral vision Side effects Treatment burden U > 80 (N = 7) Autonomy Reading details Darkness & Glare Peripheral vision Side effects Treatment burden U < 65 (N = 11) Autonomy Reading details Darkness & Glare Peripheral vision Side effects Treatment burden Page 24 © Dintsios | HTAi | Bilbao, June 25 th2012 | Glaucoma patients’