Transcript Clinical Advancement Teams
Diabetes Update - Integrating Clinical Trials with EMR Practicalities
Michael Shannon, MD PMG Endocrinology, Olympia WA
Outline of Talk
Newly released and upcoming medications: the incretins, DPP-IV inhibitors, and what’s coming Revised ADA/EASD and AACE guidelines: focus on potency, safety, cost Introduction of EPIC project at Providence Role of a Clinical Advancement Team in promoting best clinical practices
The Diabetes Toolbox 2010
Drug Class (First in Class)
Insulin Sulfonylurea (chlorpropamide) Biguanides (metformin) Alpha-glucosidase inhibitor (acarbose) Thiazolidinedione (troglitazone) Meglitinide (repaglinide) Incretins (exenatide) DPP-IV Inhibitors (sitagliptin) FDA Approval 1922 (first use) 1958 1995 1995 1997 1997 2005 2006
What’s New and What’s Coming
Incretins: GLP-1 agonists and analogs Incretins: DPP-IV inhibitors Sodium-Glucose Transport Proteins-2 (SGLT 2) inhibitors: Dapagliflozin
Glucagon-Like Peptide-1
Glucagon-like peptide-1 is an incretin, a gut hormone that increases the release of insulin Many effects of GLP-1: Increases insulin sensitivity Inhibits glucagon release Inhibits gastric emptying Increases satiety and decreases food intake Native GLP-1 improves glucose control but the short half-life limits its use (needs pump)
GLP-1 Agonists and DPP-IV Inhibitors
Mixed Meal Intestinal GLP-1 Release Active GLP-1 DPP4 Rapid Inactivation t 1/2 = 1-2 min Inactive GLP-1
GLP-1 Agonists and Analogs
Exenatide: GLP-1 receptor agonist (BID) Liraglutide: GLP-1 analog (QD) Under development: Once-weekly exenatide long-acting release (LAR) Taspoglutide Lixisenatide Others in various stages
GLP-1 Inhibitors: Exenatide
Modification of GLP-1 to prevent degrading Modest benefit in HbA1c 0.7-1.1% Significant nausea (52% vs 8% for insulin) and emesis; RJ Heine et al, Ann Int Med 2005 Some weight loss as well Significant heterogeneity in response in clinical experience (some all-stars, some fail) Safety warnings about pancreatitis, kidneys
Liraglutide
Approved January 2010; once-daily injection Associated with similar modest decrease in HbA1c of 0.7% - 1.1% with
slightly
more reduction in one trial (LEAD-6) Less renal limitations than exenatide Possible association with pancreatitis and there is suggestion of rare thyroid tumors in rats so special warnings for medullary thyroid cancer
DPP-IV Inhibitors
Sitagliptin (Januvia) and saxagliptin (Onglyza) and linagliptin (Tradjenta) Associated with modest decrease in HbA1c of 0.5% - 0.8%; can be dosed with ESRD Minimal side effects (possible more minor infections) All are pregnancy Category B – unclear why Minimal long-term safety data – possible off target interactions with diverse DPP-IV targets
SGLT-2 Inhibitors
Sodium-glucose cotransporter-2 is a protein that aids in glucose reabsorption from the kidney Natural mutation: familial renal glycosuria Inhibition of this protein leads to increased glucosuria – in early studies appears to reduce A1c and body weight, with possible side effect of increased UTIs and yeast infections Several in development (dapagliflozin filed with FDA, remogliflozin, sergliflozin)
Final Word on New Therapies
None of these have been in wide use for long Lessons of rosiglitazone: hemoglobin A1c is a surrogate endpoint, not the true goal of care None of these have any microvascular or macrovascular endpoints (trials underway) Most of these drugs cost upwards of $6/day
Interesting products – but what is their impact?
Is lowering A1c the goal of care?
Diagnosis is a fairly soft endpoint, but death is unequivocal.
Edwin AM Gale, Lancet 2003
ADA/EASD DM2 Algorithm
Updated in 2009 based on clinical trials and collective clinical judgment and experience of authors Evaluates glucose reductions, non-glycemic effects that could reduce diabetic complications, safety, tolerability, ease of use, and cost of each intervention Provides treatment algorithm with intervention tiers DM Nathan et al, Diabetes Care 2009
ADA/EASD DM2 Algorithm
Tier 1: Well validated core therapies
At diagnosis:
Lifestyle + Metformin + Basal insulin Lifestyle + Metformin + Intensive insulin Lifestyle + Metformin Lifestyle + Metformin + Sulfonylurea STEP 1 STEP 2 Tier 2: Less well validated therapies Lifestyle + Metformin + Pioglitazone STEP 3 Lifestyle + Metformin + Pioglitazone + Sulfonylurea Lifestyle + Metformin + GLP-1 agonist Lifestyle + Metformin + Basal insulin
DM Nathan et al, Diabetes Care 2009
Diabetes interventions by tiers
Tier 1 Interventions (‘well-validated core’)
Lifestyle changes with diet and exercise (1.0-2.0)* Metformin (1.0-2.0) Insulin (1.5-3.5) Sulfonylureas (1.0-2.0)
Tier 2 Interventions (‘less well-validated’ core)
Thiazolidinediones (pioglitazone) (0.5-1.4) GLP-1 agonists (exenatide) (0.5-1.0)
Others (less A1c lowering, less evidence, or costlier):
α-Glucosidase inhibitors (0.5-0.8), Glinides (0.5-1.5) Pramlintide (0.5-1.0), DPP-IV inhibitors (0.5-0.8) DM Nathan et al, Diabetes Care 2009
Comments on treatment choices
Tier 2
options may be considered when weight loss is major goal (exenatide) or when hypoglycemia is major concern (pioglitazone and exenatide, not rosi) α-Glucosidase inhibitors, glinides, pramlintide, and DPP-4 inhibitors appropriate for selected patients Starting or intensifying insulin preferred to third oral Algorithm is cautious in use of newer treatments DM Nathan et al, Diabetes Care 2009
AACE Algorithm
Released by American Association of Clinical Endocrinologists in October 2009 Stated by AACE to include a variety of choices based on first-line, second-line, and third-line therapies as well as secondary factors (weight, risk of hypoglycemia) Emphasizes wider choices Ends up somewhat overwhelming algorithm HW Rodbard et al, Endocrine Practice 2009
Diabetes Toolbox: A Critical Look
Drug Class
Sulfonylureas (glimepiride, etc) Metformin Thiazolidediones (pio 45 qday) GLP-1 agonist (exenatide 10 bid) DPP-IV (sitagliptin 100 qday) Human Insulin Insulin Analogs (vials) Insulin Analogs (pens) Drugstore.com
A1C%
1.2-2.0
1.2-2.0
0.8-1.4
0.8-1.2
0.6-0.8
No limit No limit No limit
Cost/Mo
4-12 4-12 245 271 193 ~25 ~80 ~100
Indications for Insulin Therapy
Severe hyperglycemia at diagnosis or at a later point despite aggressive treatment To meet glycemic goals - hyperglycaemia despite maximum doses of oral agents Decompensation of other organ systems that limits use of other oral agents Early cost-effective potent treatment
A Broader Toolbox Doesn’t Always Improve Clinical Outcomes
Diabetes is a progressive disease More choices can decrease ability to intensify care (SS Iyengar, 2000) Use algorithms as a guideline (joint ADA EASD consensus statement or AACE/ACE) Individual patients may have specific issues that require tailoring algorithms to their needs Guidelines need to be available and accessible!
From Trials and Guidelines to Implementing Best Practices
Providence Health & Services has 27 hospitals, major health plan, ~2000 doctors Despite this, limited ways to disseminate best practices and learn from other regions Two reasons for Clinical Advancement Teams: Collect local successes and share the team practices and order sets that allow these successes And… the entire system is going onto EPIC, for a new EMR
28
Washington
29
Pneumonia Mortality: Prov Centralia Sepsis Mortality, NOT Present on Admission, Prov Centralia Mortality on Ventilator (use on Day 1), Prov Everett Central Line Blood Stream Infections, Prov Everett Mortality on Ventilator (Use after Day 1), Prov Sacred Heart, Spokane Heart Failure Readmissions, Prov Holy Family, Spokane Sepsis Mortality, Present on Admission, Prov Holy Family, Spokane
Oregon Pneumonia Readmissions, Prov Hood River AMI Readmissions, Prov Milwaukie Neonatal Morbidity/Mortality, Prov St Vincent, Portland (infants 501-1500 grams) Heart Failure Readmissions, Prov Milwaukie TIE!
Out Patient Data Percent of patients over 65 with documented pneumococcal vaccination: Winner: PMG South Eagle Point @ 91% [near Medford OR] (Range: 26% - 91%; P H & S average: 51%) Percent of ambulatory diabetics who have not had an LDL test drawn in the past year: Winner: PMG West Linn (in West Linn, OR--South of Portland) 29% (range: 29% - 70%, P H & S average: 56%) Present of ambulatory adult diabetics with most recent HgAic > 9% who have not had a HgA1c drawn the past year: Winner: tie between PMG North Plaza [by Providence Portland medical Center Hospital in Portland] AND PMG Teaching Clinic, Milwaukie (near Providence Milwaukie) @ 12% (range: 70- 12, P H & S average: 19)
Clinical Guidance for EHR Build
Clinical Advisory Council Content Build Workflow Build As Needed Decisions • •
Clinical Advancement Teams “Think Tanks” in 32 disciplines Mainly virtual every 2 weeks; one in person orientation
• •
6 to 8 Collaborative Build Sessions Travel to Seattle April-August Physicians
•
As Needed Decisions Quick decisions, e.g. correcting an omission or typographical error Non-physician Clinicians
Clinical Advisory Council
Coordinates and oversees “Clinical Guidance” to support the Quality Strategic Framework. Core subgroups
Other task forces / workgroups as needed
Safe Medication Formulary Workgroup Interdisciplinary Content Review Physician Content Review Workgroup Clinical Decision Support Workgroup Clinical ROI Workgroup Regulatory / Accreditation Workgroup 32 specialty Clinical Advancement Teams
Clinical Advancement Teams
6 7 8 9 10 11 12
ID
1 2 3 4 5
Wave 1: Early Readiness or Long Review Cycles
Adult Primary Care Hospital Medicine Pediatrics Urgent / Immediate Care Emergency Medicine Endocrinology and Diabetes Care Obstetrics Women's Health / Breast Health / Gynecology Heart and Vascular Oncology Physiatry Palliative Care 18 19 20 21 22 23 13 14 15 16 17
ID Wave 2: Shorter Review Cycles
Dermatology Orthopedics General Surgery Pulmonary / Sleep Neurology and Stroke Neurosurgery and Spine Nephrology Pain Management / Anesthesiology Urology Gastroenterology Critical Care
I D
24
Wave 3: Delayed Readiness or Short Cycles
Behavioral Health 25 Occupational Medicine 26 Rheumatology 27 Rehabilitation Medicine 28 29 Infectious Disease / Travel Medicine Otolaryngology and Audiology 30 Wound Care 31 Radiology 32 Ophthalmology 34
Who is on a Clinical Advancement Team?
Clinical Advancement Teams
Physicians Non-physician Clinicians Ambulatory Inpatient
Endocrinology/Diabetes: 2 endos, 2 hospitalists, 3 PharmD, 3 PCPs, 3 nurse specialists, 4 CDEs, and one laboratory specialist
Inclusive “Mountain” of Subject Matter Experts
Clinical Champions SME representatives CA T Translate clinical input into the EHR Phone, email Print outs Quick conversations Section meetings hundreds of Subject Matter Experts
CAT Team: “People Skills” for EPIC
Clinical Champions SME representatives Translate clinical input into the EHR
CAT Goals to Achieve
Order sets that are usable and up to date (no, they don’t still make insulin ultralente) Workable dashboard for best clinical practices When was my last diabetic eye exam?
How few clicks to order a urine microalbumin?
Extractable data for disease management registries and (likely) for payor demands/ACO Find local successes and disseminate them
ADA/EASD DM2 Algorithm
Tier 1: Well validated core therapies
At diagnosis:
Lifestyle + Metformin + Basal insulin Lifestyle + Metformin + Intensive insulin Lifestyle + Metformin Lifestyle + Metformin + Sulfonylurea STEP 1 STEP 2 Tier 2: Less well validated therapies Lifestyle + Metformin + Pioglitazone STEP 3 Lifestyle + Metformin + Pioglitazone + Sulfonylurea Lifestyle + Metformin + GLP-1 agonist Lifestyle + Metformin + Basal insulin
DM Nathan et al, Diabetes Care 2009
Content to Review
Inpatient: Diabetic Ketoacidosis Admission Insulin drip order set Subcutaneous Insulin order sets Outpatient: Diabetes Outpatient Visit Thyroid disease Special groups: pediatrics, obstetrics
CAT Team: Identifying Barriers
Fear of loss of autonomy Fear of technology changes to workflow Generalized resistance to intrusion on “the way it’s always been” (territorial behavior)
Many ways to contribute feedback
• • • • • Add a comment to the online collaboration tool Phone / email your Clinical Champion or subject matter expert representative Discuss at a sub-section meeting or team meeting Physician liaisons / point persons: print-outs Quick conversations
Conclusion
There are interesting new therapies available and on the horizon, but all still have limited long-term safety and hard endpoint data The ADA/EASD guidelines support first-tier use of metformin, sulfonylureas, and insulin, with second-tier use of GLP-1 and pioglitazone Providence will use EPIC to take best local practices and spread success across system Clinical Advancement Teams will draw out local experts to grow best care in Providence