Adaptation of Published Heritable Thrombophilia Testing Guidelines into Local Practice

Transcription

1 Adaptation of Published Heritable Thrombophilia Testing Guidelines into Local Practice Tyler Smith, PGY-5, UBC Hematopathology Supervisor: Dr. A. Lee Collaborators: Dr. D. Pi, Dr. M. Hudoba 2011 CADTH Symposium

2 Outline Heritable thrombophilia testing (HTT) Limitations Volume and cost Guideline adaptation process VGH protocol on inpatient HTT Survey of local thrombosis experts Future directions

3 Background Thrombophilia = clot loving (Greek) Factors predisposing to thrombosis can be: Inherited Acquired = age, immobility, trauma, surgery, pregnancy, estrogens, cancer, PNH, HIT, APLAS, and more...

4 Heritable Thrombophilia Testing (HTT) Five well-recognized inherited thrombophilias: Factor V Leiden mutation Prothrombin 20210A mutation Protein C deficiency Protein S deficiency Antithrombin deficiency

5 HT: Magnitude of Risk Divided into low and high risk groups ophilia or V en ombin 10A in S ency in C ency ombin ency Gen. Pop. Incident VTE Recurrent VT Prevalence Prevalence Rel. Risk Prevalence Re 3-7% 12-20% % ( ) (1. 1-3% 3-8% % ( ) ( % 1-3% % ( ) % 2-5% % ( ) % 1-2% % ( )

6 Limitations of HTT Negative results do not exclude heritable cause Negative results do not indicate a low risk of recurrent thrombosis Acquired factors, but NOT inherited factors, are strong, independent predictors of recurrent VTE Family history and clinical features are better a determining risk of thrombosis

7 Limitations of HTT Testing is expensive ($250/patient in BC) Unselected HTT is not cost-effective 1 Assays are not standardized and are technically challenging to perform Test results are difficult to interpret Unclear how results should alter treatment Knowing the heritable thrombophilia status has not been shown to improve patient outcomes

8 HTT Indications VERY controversial topic in the literature there are no absolute indications for clinical diagnostic thrombophilia testing 1 A small 2009 survey submitted to BC thrombosis experts (10/12 = hematologists) found: 82% felt that HTT results influence patient management in <10% cases 73% sometimes order HTT even when they don think it will influence management

9 HTT Contraindications NOT very controversial topic in the literature HTT results are unreliable in patients: With acute thrombosis On anticoagulant therapy HTT is not useful in predicting arterial clots

10 HTT: Magnitude of the Problem

11 ~2000 test = ~$500K/ Volume of HTT at VGH FVL tests performed at VGH April March 2009

12 Our Synopsis of the Problem HTT is an area of confusion and overutilization Cost to the system is sufficient to warrant intervention to limit inappropriate HTT

13 HTT: Possible Solutions

14 Policy vs. Guideline Policy = compliance is mandatory More likely to encounter resistance Guideline = compliance not enforced More likely to be educational

15 HTT Guidelines May 2009 meeting of BC hematologists and hematopathologists Consensus that there is a need for a set of clear, local (BC) guidelines for HTT to help: Establish accepted indications for HTT Clarify HTT interpretation Limit HTT to situations in which the results are likely to alter management, thereby

16 Guidelines: Barriers Resources: time, effort, cost Disagreements amongst experts Each expert takes their own biopsy of the body of literature! Need to raise clinician awareness of guidelines Resistance to uptake by clinicians Perceived threat to autonomy

17 Guideline Models Traditional approach Bias Expense Time Evidence-based Consensus-based (all stakeholders) Consensus-based (experts) Expert opinion Modern approach = blend of evidence and consensus, involving local experts and stakehold

18 Guideline Adaptation A rigorous, systematic methodology in which existing guidelines are used to create locally relevant guidelines Reduces duplications of effort to achieve efficienc while maintaining the validity of recommendation Fosters local ownership of guideline recommendations to promote utilization Useful as a vehicle for inter-provincial collaborati

19 ADAPTE Collaboration An international collaboration of researchers and guideline developers who aim: To promote the development and use of clinic practice guidelines through the adaptation of existing guidelines To develop and validate a generic adaptation process that will foster valid and high-quality adapted guidelines as well as the users sense of ownership of the adapted guideline.

20 Our Objectives To implement a local policy and guideline to reduce inappropriate HTT for the inpatient setting To adapt published guidelines for the outpatient setting with input from BC experts and stakeholders using ADAPTE framework

21 Methodology (1) For inpatient HTT at VGH: Consulted with VGH hematologists Created flow chart and pre-printed order (PPO) form for HTT Instituted as policy (i.e. HTT not performed without PPO) Collected data on who is ordering HTT

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24 Methodology (2) Following ADAPTE process: Searched Pubmed for HTT guideline set with balanced summary of literature Brit J Haem (2010) 149(2):

25 Methodology (3) ADAPTE: External review by target audience transformed BJH 2010 HTT Guidelines into a survey questionnaire Survey ed to BC experts to gather consensus o individual recommendations Each recommendation scored on 5-point Likert scale +2 = strongly agree, +1 = agree, 0 = neutral, -1 = disagree, -2 = strongly disagree, N/A Mean score used to determine consensus = strong, = moderate,

26 Project Results

27 Effect on Inpatient HTT PPO Instituted

28 TT Guideline BC Survey Issued by July 20, 2010 Closed Aug 31, of 31 specialists participated in survey 16 adult hematologists (of 19) 1 pediatric hematologist (of 1) 2 hematopathologists (of 7) 1 general internist (of 1)

29 HTT Survey Results Consensus scoring results: Strong = 15/30 (50%) recommendations Moderate = 10/30 (33%) recommendations Poor = 5/30 (17%) recommendations Overall, 25/30 (83%) moderate or strong consensus

30 0 HTT Survey Results Strong consensus was seen for statements w strong evidence (level 1A or 1B) and weaker consensus for areas with weaker evidence Number of Statements Grade 1A or 1B Grade 2B or 1C Grade 2C or C

31 Project Limitations Most input from adult hematologists, but need to involve stakeholders (i.e. the people who order most HTT!)

32 Project Limitations Unable to measure impact on patient outcome Requires dedicated leadership and content expertise Does not address ongoing monitoring of scientific advancement and update of guidelines

33 Future Directions

34 Future Plans Our ultimate goal is to develop BC practice guidelines by adapting the British guideline recommendations that had moderate or strong consensus To maximize acceptance and utilization, we will: Obtain feedback on a draft document from hig volume users (e.g. GPs) Review feedback and revise as appropriate Develop user-friendly tools that will help users

35 Publish survey results and guidelines (BCMJ) Future Plans Arrange stakeholder panel to review these guidelin and user-friendly tools Must include representation from hematology, fa medicine, internal medicine, obstetrics, & neuro Seek guideline partnership or endorsement with Guidelines and Protocols Advisory Committee (GP Currently, the Clinical Practice Committee is reviewing HTT ordering patterns of GPs

36 Conclusions HTT is expensive and has limited clinical utility A combination approach by using policy and guideline adaptation best addresses usage patterns in different settings Our project demonstrates that cost savings from optimal test utilization can be realized without significant resource costs Further work is required to meet our objectives and address current limitations

37 Acknowledgments Dr. Agnes Lee: Supervisor Dr. David Pi: Inspiration, VGH HTT data Dr. Monika Hudoba: VGH HTT forms Dr. Bakul Dalal: GPAC planning Dr. George Browman: Guideline adaptation Jason Pal: Excel spreadsheets And all survey participants...

38 Sample Guidelines Guide to Heritable Thrombophilia Testing (HTT) in Women onsidering Estrogen-Containing Oral Contraceptive Pill Therapy counseling women with prior VT regarding oral contraception, one should mmend considering an alternative contraceptive or transdermal HRT witho g HT testing, as a negative test result does not exclude an increased risk o unseling women with a first degree relative with unprovoked VT and a high e. deficiency of AT, PC, PS) regarding oral contraception, HT testing may a VT risk assessment and contraceptive recommendations. unseling women with a first degree relative with unprovoked VT and a low T (i.e. FVL or PTGM) regarding oral contraception, one should recommend sidering an alternative contraceptive or transdermal HRT without offering H testing, as a negative test result does not exclude an increased risk of VT. ounseling a woman with a first degree relative with unprovoked VT and eith ive or unknown HT status regarding oral contraception, one should sugges der alternative contraception or transdermal HRT and that HTT is not indica

39 Sample Guidelines

40 HTT Indications VERY controversial topic in the literature there are no absolute indications for clinical diagnostic thrombophilia testing 1 idiopathic or recurrent thrombosis...young age (< 40 years)...positive family history... thrombosis in unusual vascular territory 1 unprovoked VTE at any age 2

41 HTT in Inpatients Functional assays for PS, PC, and AT deficiencie are influenced by numerous factors Anticoagulants, acute clot, vitamin K deficiency DIC, liver disease, pregnancy, and others Abnormal results lead to repeat testing and mislabeling of patients

42 VGH Inpatient HTT April March 2009 Total Patients (N) Below Normal (Mild)* (N) Below Normal (Marked)* (N) Lack Confounding Conditions** (N) T C ildly abnormal results - AT ( ), PC ( ). Markedly abnormal results: AT (<0.5), PC (<0.5). onfounding Conditions - additional laboratory test profile suggestive of a concurrent clinical

43 VGH Inpatient HTT: Who s Ordering?