Follow-up GISELA LILJA

Transcription

1 Follow-up GISELA LILJA

2 Outcome in the TTM 2 trial Primary outcome Survival Secondary outcome Overall social functioning Patient-reported health (quality of life) Tertiary outcome Detailed information on neuro-cognitive functioning Long-term follow-up

3 Time-points

4 TTM 2 Follow-up time-points At 30 days (telephone) At 6 months (face-to-face) At 24 months (face-to-face)

5 Outcome Assessments

6 TTM 2 Outcome Assessments Clinician-reported outcome Glasgow Outcome Scale (GOS) Glasgow Outcome Scale Extended (GOSE)

7 History GOS and CPC 1975 The Glasgow Outcome Scale (GOS) after brain injury first described. Jennett & Bond. Lancet, The GOS recommended world-wide to enable comparisons between studies. McMillan et al. Nature reviews Neurology, The first follow-up/review article observations of the use of the GOS Jennett et al. J Neurol Neurosurg Psych Detailed descriptions of each category Patients that regain consciousness; three upper levels divided into better/worse (8 categories) Pre-traumatic state important to not overestimate effects of brain injury or compare to when it was at worst The importance of mental/personality changes in addition to more obvious physical limitations 1986 BRCT-study. GOS (OPC) used together with a modified version of the same scale to assess cerebral consequences only; the Cerebral Performance Category (CPC) scale. BRCT I study group. Am J Emer Med, 1986 Both scales REQUIRED

8 CPC in Resuscitation trials 1991 First Utstein guidelines: Recommendation to use GOS as both OPC and the CPC >1991 This recommendation widespread attention. But on the road the OPC/GOS disappeared 1997 Second Utstein guidelines: CPC criticised

9 Improvment of the original GOS scale The original 5 category scale found too broad to reflect important differences/changes The extended 8 point version (GOSE) increased attention. Jennett et al. J Neurol Neurosurg Psych,1981 Disability as an effect of brain injury; change from pre-event state or due to mental/physical impairment Wilson et al. J Neurotrauma, 1998 Low inter-rater reliability affects comparisons of outcome between multiple raters and sites A standardized structured interview (GOS and GOSE) improved inter-rater agreement to 92% and increased attention to mental aspects Wilson et al. J Neurotrauma, 1998 Those involved in acute care should not evaluate GOS in research. Anderson et al. Brain Inj, 1993 Use best source of information available (patient, relative, other informant) Wilson et al. J Neurotrauma, 1998 On-going training of raters. Ekegren et al. Injury, Int J.Care Injured, 2015 Binary categorization (independent/dependent) insensitive to detect clinically relevant changes GOSE more sensitive to change than GOS Using all categories in (ordinal) statistical analyses increase sensitivity. Levin et al. J Neurotrauma, 2001; Teasdale et al. J Neurotrauma, 1998; Weir et al. J of Neurotrauma, 2012; McMillan et al. Nature reviews Neurology, 2016

10 Improvment of the original GOS scale The original 5 category scale found too broad to reflect important differences/changes The extended 8 point version (GOSE) increased attention. Jennett et al. J Neurol Neurosurg Psych,1981 Disability as an effect of brain injury; change from pre-event state or due to mental/physical impairment Wilson et al. J Neurotrauma, 1998 Low inter-rater reliability affects comparisons of outcome between multiple raters and sites A standardized structured interview (GOS and GOSE) improved inter-rater agreement to 92% and increased attention to mental aspects Wilson et al. J Neurotrauma, 1998 Those involved in acute care should not evaluate GOS in research. Anderson et al. Brain Inj, 1993 Use best source of information available (patient, relative, other informant) Wilson et al. J Neurotrauma, 1998 On-going training of raters. Ekegren et al. Injury, Int J.Care Injured, 2015 Binary categorization (independent/dependent) insensitive to detect clinically relevant changes GOSE more sensitive to change than GOS Same problems as described for the CPC GOS improved during time (>30 years) These improvements never followed the CPC since the CPC had become a scale of it s own Using all categories in (ordinal) statistical analyses increase sensitivity. Levin et al. J Neurotrauma, 2001; Teasdale et al. J Neurotrauma, 1998; Weir et al. J of Neurotrauma, 2012; McMillan et al. Nature reviews Neurology, 2016

11 Improvment of the original GOS scale The original 5 category scale found too broad to reflect important differences/changes The extended 8 point version (GOSE) increased attention. Jennett et al. J Neurol Neurosurg Psych,1981 Disability as an effect of brain injury; change from pre-event state or due to mental/physical impairment Wilson et al. J Neurotrauma, 1998 Low inter-rater reliability affects comparisons of outcome between multiple raters and sites A standardized structured interview (GOS and GOSE) improved inter-rater agreement to 92% and increased attention to mental aspects Wilson et al. J Neurotrauma, 1998 Those involved in acute care should not evaluate GOS in research. Anderson et al. Brain Inj, 1993 Use best source of information available (patient, relative, other informant) Wilson et al. J Neurotrauma, 1998 On-going training of raters. Ekegren et al. Injury, Int J.Care Injured, 2015 Binary categorization (independent/dependent) insensitive to detect clinically relevant changes GOSE more sensitive to change than GOS Same problems as described for the CPC GOS improved during time (>30 years) GOS and GOSE These improvements Improves inter-rater never followed reliability the CPC since Provide the CPC a better had become structure/help a scale offor it sscoring own Higher ability to detect change Using all categories in (ordinal) statistical analyses increase sensitivity. Levin et al. J Neurotrauma, 2001; Teasdale et al. J Neurotrauma, 1998; Weir et al. J of Neurotrauma, 2012; McMillan et al. Nature reviews Neurology, 2016

12 CPC GOS GOSE 1. Good cerebral performance: conscious, alert, able to work, might have mild neurologic or psychological deficit. 5. Good recovery: Resumption of normal activities even though there may be minor neurological or psychological deficits. 8. Upper good recovery 7. Lower Good recovery 2. Moderate cerebral disability: conscious, sufficient cerebral function for independent activities of daily life. Able to work in sheltered environment 4. Moderate disability: (Disabled but independent). Patient is independent as far as daily life is concerned. The disabilities found include varying degrees of dysphasia, hemiparesis, or ataxia, as well as intellectual and memory deficits and personality changes. Some previous activities, either at work or with social life is no longer possible. Some patients are able to return to certain kinds of jobs that does not involve high levels of performance in the area of their major deficit. 6. Upper Moderate Disability 5. Lower Moderate Disability 3. Severe cerebral disability: conscious, dependent on others for daily support because of impaired brain function. Ranges from ambulatory state to severe dementia or paralysis. 3. Severe disability: (Conscious but dependent). Patient depends upon others for daily support due to mental or physical disability or both. 4. Upper Severe Disability 3. Lower Severe Disability 4. Coma or vegetative state 2. Persistent vegetative state: Patient exhibits no obvious cortical function 2. Vegetative state 5. Death 1. Death 1. Death

13 TTM 2 Outcome Assessments Clinician-reported outcome Glasgow Outcome Scale (GOS) Glasgow Outcome Scale Extended (GOSE) modified Rankin Scale (mrs)

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15 mrs- 9 questions

16 mrs calculator

17 Outcome Assessments TTM 2 Patient-reported outcome EuroQol-5 Dimension-5 Levels (EQ-5D-5L)

18 EQ-5D-5L 5 questions index

19 EQ-5D-5L VAS

20 Outcome Assessments TTM 2 Patient-reported outcome EuroQol-5 Dimension-5 Levels (EQ-5D-5L) Two Simple Questions (TSQ)

21 Outcome Assessments TTM 2 Patient-reported outcome EuroQol-5 Dimension-5 Levels (EQ-5D-5L) Two Simple Questions (TSQ) Life satisfaction

22 Life Satisfaction All things considered, how satisfied are you with your life as a whole these days? Range 1-10: Completely dissatisfied to completely satisfied world value questionnaire

23 Outcome Assessments TTM 2 Observer-reported outcome

24 Outcome Assessments TTM 2 Observer-reported outcome Informant Questionnaire on Cognitive Decline (IQCODE)

25 Outcome Assessments TTM 2 Observer-reported outcome Informant Questionnaire on Cognitive Decline (IQCODE) A psychometric evaluation based on data from TTM1 justifies the modified version and it s use for this population NEW! Use both as both: 1. At ICU/baseline =pre-arrest decline over past 5 years, 16 items original version Previous use of IQCODE at ICU e.g. Pisani et al. J Am Geri Soc, 2003; Panharipande,et al. NEJM, At follow-up (compared to before cardiac arrest, 26 items modified version)

26 Outcome assessments TTM 2 Performance outcome Montreal Cognitive Assessment (MOCA) Symbol Digit Modalities Test (SDMT)

27 Patient characteristics at 180 days TTM2 Native language Education Previous problems Place of stay Place of follow-up Pre and post arrest occupation (retirement) Living situation (as married or alone) Rehabilitation provided Cardiovascular riskfactors

28 Patient characteristics at 180 days TTM2 Native language Education Previous problems Place of stay Place of follow-up Pre and post arrest occupation (retirement) Living situation (as married or alone) Rehabilitation provided Cardiovascular riskfactors

29 Cardiovascular riskfactors TTM 2 Framingham risk scores HBA1C Total cholesterol HDL cholesterol Smoker? Diabetes? Systolic blood pressure Treatment for high blood pressure? Length/weight (BMI) Physical activity Two questions (based on AHA recommendations for phyiscal activity, 2007) 30 seconds chair stand test (?) Time-frame ±1 month

30 Outcome follow-up in the TTM 2 trial Primary outcome Survival yes/no at 180 days Secondary outcome Overall social functioning by an all level GOSE at 180 days Patient-reported health (quality of life) EQ-5D-5L at 180 days Tertiary outcome Overall social functioning by GOS (30 days) and mrs (30 day and 6 months) Detailed neuro-cognitive functioning by MOCA, SDMT,TSQ and IQCODE at 180 days Long-term follow-up at 24 months by GOSE, EQ-5D-5L, MOCA, SDMT, TSQ, IQCODE

31 Key to success A strong belief by all that these outcomes ARE important in addition to the primary outcome of dead or alive All includes investigators, examiners, patients, relatives and all others involved

32 What s needed? - Extensive efforts by ALL to minimise missing data. Important to include as many as possible! - Face to face follow-ups in the majority - Ability to perform alternative follow ups when needed as visiting patients at their nursing home - telephone follow-ups only when no other option - Understanding the importance of training and the need to carefully study follow-up manuals and test instructions - in order to increase inter-rater reliability and avoid possible bias of test results - Instantly report to the follow-up team when problems are identified - immediate support in order to increase high levels of inclusion and high-quality data

33 Questions? Comments? Suggestions?

34 Sub-studies JOSEF DANKIEWICZ

35 TTM1 A lot of publications Sub-studies (Cognitive, EEG..) Post-hoc analyses Biobank

36 Biobank To be funded! Ideally admission, 24, 48, 72h after arrest. Genetics (with comparison group) No missing samples due to early deaths.

37 Post-hoc analyses

38 Sub-studies Sub-studies pre-defined. Protocol mandated (published) Approved by SG 1 Coordinating site and investigator ecrf harmonisation.

39 Post-hoc Do not need to be pre-defined Protocol optional (encouraged) Approved by SG 1 Coordinating investigator (PhD-authors?) ecrf harmonisation. Proposal form

40 Post-hoc Background Hypothesis Patients Outcome Data from the ecrf Preliminary statistical analysis.

41 Timeline How do we proceed? HANS FRIBERG

42 Timeline depends on funding (Dec 7) 2016 Trial design, ethics application, site recruitement 2017 Patient recruitement, run-in period, site initiations Patient recruitement and interim analysis 1 & Presentation of results, long-term follow-up 2022 Presentation of long-term outcomes

43 Plan for site recruitement Inventory ongoing Requirements fulfilled? Application form mandatory Decision by SG who will finally participate depends on: Funding Reasonable balance Other factors Ethical approvals Insurance issues Site visits and initiator meetings

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