An update from the HISTORIC initiative

Transcription

1 DEPARTMENT OF DERMATOLOGY, ROSKILDE, DENMARK An update from the HISTORIC initiative Linnea Thorlacius, MD, PhD student CSG-COUSIN, Berlin, January 9

2 DEPARTMENT OF DERMATOLOGY, ROSKILDE HOSPITAL, DENMARK AGENDA Hidradenitis suppurativa - a deliberating skin disease The HISTORIC initiative Method Preliminary results Discussion

3 HIDRADENITIS SUPPURATIVA (HS): Is a chronic, inflammatory skin disease, characterised by repeated outbreaks of painful inflamed lesions in the apocrine gland-bearing regions Has an estimated prevalence of 1-4 % worldwide Is associated with significant disability and handicap due to pain and subsequent loss of mobility Is often accompanied by embarrassment, disabling social stigma, low self-worth and a strong negative impact on interpersonal relationships, education and work

4 BACKGROUND Reported outcome measures for HS are numerous and diverse A recent systematic review found a total of 30 outcome measure instruments in 12 RCTs 90 % of these outcome measure instruments lacked any form of validation data

5 HISTORIC

6 First HISTORIC goal Aim To develop a Core Outcome Set (COS) suitable for trials on the management of HS. All types of interventions for all HS patients are targeted by the COS, regardless of setting or mode of administration.

7 METHOD DEPARTMENT OF DERMATOLOGY, ROSKILDE HOSPTIAL, DENMARK

8 Stakeholder involvement 6 groups of stakeholders were invited: 1.Patients 2.Dermatologist HS 3.Surgeons HS 4.Nurses HS specialist 5.Industry representatives 6.Drug regulatory authorities A 1:1 ratio of patients: health care professionals (HCPs) was aimed for Participants (Accepted/Invited) HS Experts 59/138 -Medical 49/120 -Surgical 3/11 -Nursing 4/7 Patients 45/58 Industry 2/2 Regulatory 1/3 Total 104/196 Countries 19/23 Continents 5/4.

9 Delphi Round 1: Online 9 days August Please rate each of the following outcomes listed on their importance in being measured as an outcome in all clinical trials for HS. The following scale may be used to rate importance: 1-3: not important to measure in all clinical trials for HS 4-6: important, but not essential to measure in all clinical trials for HS 7-9: essential to measure in all clinical trials for HS You may also provide a brief rationale for your score on any item. You may also suggest a modification of definition or wording of any item. You may also add any outcome which you feel are missing from the list shown, and score them using the same scale

10 Item number Item name Patients N Patients Sum Patients Proportion critical HCPs N HCPs Sum HCPs Proportion critical Combined Proportion Colour code 36 Pain , ,962 94% Green 34 Health related Quality of life , ,904 90% Green 51 Flare frequency , ,885 88% Green 52 Inflammatory lesion count , ,904 84% Green 17 Number of abscesses , ,885 81% Green 25 Emotional well-being , ,712 77% Green 19 Psychosocial functioning , , % Green 33 Psychological functioning , ,731 77% Green 7 Satisfaction with treatment , ,712Green76% Green 13 Adverse effects of medical treatments , ,750 76% Green 28 Progression of course , ,712 75% Green 24 Time to recurrence , ,712 74% Green 32 Number of inflamed nodules , ,865 77% Yellow 44 Number of sinus tracts , ,865 77% Yellow 35 Number of fistulae , ,885 76% Yellow 12 Ability to work or study , ,692 74% Yellow 18 Total lesion count , ,769 72% Yellow 2 Drainage , ,731 71% Yellow 8 Adverse effects of surgical treatments , ,673 71% Yellow 26 Decreased mobility , ,596 70% Yellow 47 Satisfaction with care Delphi , ,615 70% Yellow 23 Impact on close relationships , , % Yellow 9 Number of cysts , ,596 67% Yellow 43 Physcian global evaluation , ,712Yellow 65% Yellow 5 Coping , ,462 64% Yellow 21 Need for treatment and bandages , ,500 63% Yellow 56 Sleep-disturbance , ,385 56% Yellow 38 Fatigue , ,346 55% Yellow 48 Independence , ,308 54% Yellow 31 Anatomic location , ,673 63% Red 22 Surface area , ,635 63% Red 46 Compliance , ,654 62% Red 40 Patient global evaluation , ,692 60% Red 6 Odour , ,519 58% Red 11 Intimacy , ,481 56% Red 90 % 42 Ulceration , ,558 56% Red 20 Scarring from HS , ,462 55% Red 54 Constitutional symptoms response , ,462 55% Red 49 Time to post-op recovery , ,365 52% Red rate 10 Comorbidities , ,423 52% Red 4 Economic burden , ,442 52% Red 45 Scarring from surgery , ,365 49% Red 3 Edema , ,308 49% Red 14 Number of non-inflammed nodules , ,404 43% Red 37 Cognitition , ,269 42% Red 50 Clothing restrictions , ,212 41% Red 29 Recreation and leisure activity , ,327 41% Red 27 Satisfaction with social roles , ,346 40% Red 16 Self treatment; not prescribed , ,173 40% Red 55 Erythema , ,423 39% Red 15 Itch , ,250 38% Red 39 Cosmesis , ,308 37% Red 41 Washing or Bathing , ,231 36% Red 1 Biomarkers , ,288 32% Red 53 Comedones , ,154 28% Red 30 Dyspigmentation , ,058 16% Red 27 Red

11 DEPARTMENT OF DERMATOLOGY, ROSKILDE HOSPTIAL, DENMARK Delphi Round 2: Online 13 days September Dear Delphi participant, Thank you again for participating in this important initiative. In the next pages you will find the number of respondents and distribution of scores for each item for patients and health care professionals (HCPs). You will also find your own score from the first round. Please consider the responses from the other participants and score rate each item again. You can decide to keep your score the same or to change it. You can comment if you would want to

12 Sted og dato Dias 12 Patients Proportion Critical DEPARTMENT OF Combined DERMATOLOGY, ROSKILDE HOSPTIAL, DENMARK HCPs Proportion critical Round 1 Colour code Round 2 Colour code Item Proportion Critical Flare_frequency 1,000 0,958 98% Green Green Pain 0,947 0,979 96% Green Green Inflammatory_lesion_count 0,921 0,917 92% Green Green Health_related_Quality_of_life 0,895 0,938 92% Green Green Number_of_abscesses 0,868 0,938 90% Green Green Number_of_sinus_tracts 0,842 0,896 87% Yellow Green Number_of_fistulae 0,737 0,979 86% Yellow Green Adverse_effects_of_medical_treatments 0,895 0,813 85% Green Green Satisfaction_with_treatment 0,842 0,854 85% Green Green Time_to_recurrence 0,842 0,842 84% Green Green Number_of_inflamed_nodules 0,763 0,917 84% Yellow Green 19 Drainage 0,816 0,857 84% Yellow Green Emotional_well-being 0,842 0,792 82% Green Green Psychosocial_functioning 0,816 0,813 Green 81% Green Green Psychological_functioning 0,868 0,750 81% Green Green Total_lesion_count 0,737 0,875 81% Yellow Green Progression_of_course 0,842 0,750 80% Green Green Ability_to_work_or_study 0,816 0,750 78% Yellow Green Anatomic_location 0,711 0,771 74% Red Green Number_of_cysts 0,868 0,667 77% Yellow Yellow Delphi 2 Decreased_mobility 0,895 0,625 76% Yellow Yellow Satisfaction_with_care 0,816 0,667 74% Yellow Yellow Adverse_effects_of_surgical_treatments 0,763 0,667 71% Yellow Yellow Patient_global_evaluation 0,684 0,729 71% Red Yellow Physician_global_evaluation 0,658 0,729 69% Yellow Yellow 15 Surface_area 0,658 0,708 68% Red Yellow Compliance 0,737 0,625 68% Red Yellow Odour 0,763 0,542 Yellow 65% Red Yellow Coping 0,763 0,479 62% Yellow Yellow Number_of_chronic_areas 0,763 0,458 61% Yellow Constitutional/Prodromal_symptoms 0,763 0,396 58% Red Yellow Sleep-disturbance 0,763 0,396 58% Yellow Yellow Independence 0,842 0,208 53% Yellow Yellow Fatigue 0,711 0,313 51% Yellow Yellow Impact_on_close_relationships 0,684 0,625 65% Yellow Red Ulceration 0,632 0,604 62% Red Red Comorbidities 0,658 0,438 55% Red Red Need_for_treatment_and_bandages Attrition: 0,658 0, % Yellow Red Scarring_from_HS 0,632 0,458 54% Red Red Intimacy 4 Patients, 0,632 0,375 Red 50% Red Red Economic_burden 0,579 0,417 50% Red Red Time_to_post-op_recovery 0,632 0,292 46% Red Red Edema 2 HCPs 0,605 0,204 40% Red Red Clothing_restrictions 0,658 0,125 39% Red Red Scarring_from_surgery (7%) 0,526 0,229 38% Red Red Number_of_non-inflamed_nodules 0,368 0,368 37% Red Red Self_treatment;_not_prescribed 0,553 0,146 35% Red Red Biomarkers 0,368 0,306 34% Red Red Cognition 0,500 0,167 33% Red Red Erythema 0,368 0,271 32% Red Red Recreation_and_leisure_activity 0,474 0,125 30% Red Red Itch 0,421 0,167 29% Red Red Cosmesis 0,395 0,167 28% Red Red Washing_or_Bathing 0,474 0,083 28% Red Red Satisfaction_with_social_roles 0,289 0,104 20% Red Red Comedones 0,289 0,063 18% Red Red

13 HISTORIC consensus meetings I and II 39 participants from 13 countries and 4 continents

14 DEPARTMENT OF DERMATOLOGY, ROSKILDE, DENMARK HISTORIC consensus meetings I and II Main tasks Marking of items for exclusion Grouping if items into domains Mixture of formal presentations and group work based on nominal group theory

15 DEPARTMENT OF DERMATOLOGY, ROSKILDE HOSPTIAL, DENMARK Items marked for exclusion Item Self-treatment - not prescribed Biomarkers Cosmesis Washing or bathing Comedones Dyspigmentation Satisfaction with care Economic burden Comorbidities Reasoning for exclusion Too non-specific, difficult to measure For HS, there is no biomarker proven to be strongly related to disease activity and treatment response Participating patients felt that this items was not as important as other items, and felt that cosmesis was coved by other items such as scarring and number of sinus tracts Very individual. Could be an instrument to measure drainage, but would then be covered by the drainage item Participants, especially patients, felt that this item was not important enough to be a core outcome for trials Participants, especially patients, felt that this item was not important enough to be a core outcome for trials Not likely to be directly affected as an outcome by any intervention. and often depends on individual doctor-patient relationships. Difficult to measure, varies a lot from country to country, in trials treatment expenses are covered Not fair to include comorbidities as core outcomes as some treatments might improve HS but not the comorbidities. Comorbidities that might result from treatment should be captured as adverse events.

16 DEPARTMENT OF DERMATOLOGY, ROSKILDE HOSPTIAL, DENMARK Domains created with included items Domain Included items 1. Disease course Progression of course, Time to recurrence, Flare frequency, Number of chronic areas 2. Physical signs Total lesion count, Inflammatory lesion count, Inflamed nodules, Non-inflamed nodules, Abscesses, Fistulae, Sinus tracts, Ulceration, Edema, Cyst, Erythema, Anatomic location, Surface area, Scarring from HS, 3. HS specific quality of life Coping, Emotional well-being, Sleep, Work/study, Independence, Satisfaction with social roles, Psychosocial functioning, Psychological functioning Intimacy, Recreation, Close relationships, Cognition, Clothing restrictions, Physical functioning* 4. Satisfaction Satisfaction with treatment, Compliance, Adverse effects of drugs & surgery, Scarring from surgery, Healing time, Need for treatment/bandages 5. Symptoms Constitutional/prodromal, Fatigue, Itch, Odour, Drainage 6. Pain Pain 7. Global assessment Patient global assessment, Physician global assessment

17 DEPARTMENT OF DERMATOLOGY, ROSKILDE HOSPTIAL, DENMARK

18 Combined Domain Item Proportion Proportion Critical Proportion critical critical Colour code Colour code Progression of course Progression of course 0,828 0,855 0,8415 Green Green Progression of course Time to recurrence 0,828 0,834 0,831 Green Green Progression of course Flare frequency and duration 0,857 0,833 0,845 Green Green Progression of course Number of chronic areas 0,857 0,583 0,72 Yellow Yellow Satisfaction Time to heal 0,429 0,250 0,3395 Red Red Satisfaction Need for treatment and bandages 0,485 0,230 0,3575 Red Red HS specific QOL Coping 0,715 0,292 0,5035 Yellow Yellow HS specific QOL Intimacy 0,600 0,437 0,5185 Red Red HS specific QOL Ability to work or study 0,857 0,667 0,762 Green Yellow HS specific QOL Psychosocial functioning 0,829 0,626 0,7275 Green Yellow HS specific QOL Impact on close relationships 0,628 0,458 0,543 Red Red HS specific QOL Emotional well-being 0,857 0,604 0,7305 Green Yellow HS specific QOL Physical functioning 0,914 0,812 0,863 Yellow Green HS specifc QOL Satisfaction with social roles 0,286 0,125 0,2055 Red Red DEPARTMENT Patients OF DERMATOLOGY, HCPs ROSKILDE Round HOSPTIAL, 2 DENMARK Round 3 HS specific QOL Recreation and leisure activity 0,457 0,146 0,3015 Red Red HS specific QOL Psychological functioning 0, ,647 0,738 Green Yellow HS specific QOL Health related Quality of life 0,915 0,917 0,916 Green Green HS specific QOL Cognition 0,514 Green 0,021 0,2675 Red Red HS specific QOL Independence Third 0,686 0,105 0,3955 Yellow Red HS specific QOL Clothing restrictions 0,399 0,042 0,2205 Red Red HS specific QOL Sleep-disturbance Delphi 0,714 0,292 0,503 Yellow Yellow Physical signs Edema 0,343 0,063 0,203 Red Red Physical signs Number of cysts 0,829 0,688 0,7585 Yellow Yellow Physical signs Number of non-inflamed nodules 0,257 0,333 0,295 Red Red Physical signs Number of abscesses 0,743 0,937 0,84 Green Green Physical signs Total lesion count 0,772 0,897 0,8345 Green Green Physical signs Scarring from HS 0,428 0,355 0,3915 Red Red Physical signs Surface area 0,628 0,771 0,6995 Yellow Yellow Physical signs Anatomic location 0,800 0,834 0,817 Green Green Physical signs Number of inflamed nodules 0,828 0,979 0,9035 Green Green Physical signs Number of fistulae 0, ,938 0,912 Green Green Physical signs Ulceration 0,628 0,646 0,637 Red Red Physical signs Number of sinus tracts 0,858 Yellow 0,814 0,836 Green Green Physical signs Inflammatory lesion count 0,886 1,000 0,943 Green Green Physical signs Erythema 0,371 0,209 0,29 Red Red Pain Pain 0,943 1,000 0,9715 Green Green Symptoms Drainage Attrition: 0,800 0,834 0,817 Green Green Symptoms Odour 0,714 0,437 0,5755 Yellow Yellow Symptoms Fatigue 0,799 0,354 0,5765 Yellow Yellow Symptoms Prodromal 3 Patients, 0,742 0,334 0,538 Yellow Yellow Symptoms Itch Red Global assessment Patient global 0 HCPs 0,600 0,750 0,675 Yellow Yellow Global assessment Physician global 0,629 0,875 0,752 Yellow Yellow Marked for exclusion Self-treatment, not prescribed 0,343 0,021 0,182 Red Red (3.5 %) Marked for exclusion Biomarkers 0, ,167 0,2125 Red Red Marked for exclusion Cosmesis 0,286 0,021 0,1535 Red Red Marked for exclusion Washing or bathing 0,371 Red0 0,1855 Red Red Marked for exclusion Comedones 0,200 0,042 0,121 Red Red Marked for exclusion Dyspigmentation 0, ,0435 Red Red Marked for exclusion Satisfaction with care 0,657 0,376 0,5165 Yellow Red Marked for exclusion Economic burden 0,542 0,313 0,4275 Red Red Marked for exclusion Comorbidities 0,657 0,313 0,485 Red Red Marked for exclusion Compliance 0,486 0,334 0,41 Yellow Red Marked for exclusion Sted og dato Satisfaction with treatment 0,628 0,521 0,5745 Green Red Marked for exclusion Dias 18 Adverse effects of medical 0,572 0,604 0,588 Green Red Marked for exclusion Adverse effects of surgical 0,543 0,438 0,4905 Yellow Red Marked for exclusion Scarring from surgery 0,314 0,084 0,199 Red Red

19 DEPARTMENT OF DERMATOLOGY, ROSKILDE HOSPTIAL, DENMARK NEXT STEPS Consensus meeting Consensus meeting

20 DEPARTMENT OF DERMATOLOGY, ROSKILDE HOSPTIAL, DENMARK Discussion points When in the COS development process are domains best defined and by whom Outcomes vs. domains vs. items Advantages and disadvantages of broad vs specific outcomes/domains

21 Thank you for you attention DEPARTMENT OF DERMATOLOGY, ROSKILDE, DENMARK Linnea Thorlacius, MD, PhD student,