Sanofi U.S. Medical Affairs Request for Proposal

Transcription

1 Sanofi U.S. Medical Affairs Request for Proposal Date: July 23 rd, 2015 Disease State: Diabetes Therapeutic Area: Diabetes Area of Interest: Post-prandial glucose control for current basal insulin patients Internal Requestor Information: Name: Terry Dex, PharmD Title: Sr. Director, IME, Diabetes Phone: Fax: TAG ID #: PL-FNSQF Due Date: no later than 5PM EST on September 30 th, 2015 Health Care Gap The Centers for Disease Control and Prevention estimates that 29.1 million Americans have diabetes in 2014 with type 2 diabetes accounting for % of those cases in adults. 1 The progressive nature of type 2 diabetes requires timely optimization of treatment and ensuing β cell decline predicts that all patients will eventually require insulin replacement therapy to achieve HbA1c targets. 2,3,4,5 In the setting of failure of one or more prior oral therapies, very few patients can expect to attain HbA1c goals because oral agents have demonstrated limited efficacy with expected HbA1c reductions of approximately.5-1.0% from a baseline of 8.0%, 12 months after supplementing failed monotherapy. 6 The ADA recommends an HbA1c of <7% for most patients, with fasting plasma glucose (FPG) targets at <130mg/dl and peak post-prandial glucose (PPG) targets <180mg/dl. 2 Current studies suggest that as high as 60% of patients taking basal insulin are unable to reach A1c goals, implying that additional therapies are required. 5,6,7,8,9 A study by Shah et al. reported that less than 50% of patients with high A1c levels had intensification of their regimens irrespective of specialty type. 11 While specialists were more aggressive in prescribing insulin than their general practitioner counterparts in that study, all areas of clinical practice tend to delay insulin use, corroborated by survey data from >66,000 diabetes patients worldwide where average A1c levels at insulin initiation were 9.5% with over 90% of these patients already reporting some type of complication. 11,12 In addition, a post-hoc analysis of 3 insulin titration trials has demonstrated that FPG reduction becomes proportionally smaller with increasing doses of basal insulin, leveling at ~ 0.5 IU/kg, suggesting a dose-response curve for basal insulin and the necessity of monitoring FPG levels for appropriate insulin titration. 37 Progressive diminution of insulin secretory capacity for patients on basal insulin often leads to an additional requirement for prandial control frequently satisfied by the addition of rapid-acting 2,4,9, 13,14,15, 16, 17,18 insulins. Barriers to the use of rapid acting insulin s include fear of hypoglycemia, multiple daily injections, dosing inflexibility and weight gain. 19,20 An alternative intensification strategy to manage post-prandial glucose excursions which subscribes to the 2015 EASD/ADA position statement recommendations, is to utilize a GLP-1RA. 2 The combination of a GLP-1RA and basal insulin has become well established after several studies confirmed non- inferior efficacy to more complex multi-dose insulin regimens, but with less hypoglycemia and with weight loss instead of weight gain. 2,7,8,10,13,21,22,23,24,25,26,27,28,29,30,31,32,33,34,35 The GLP-1 receptor agonists vary in their clinical effects due to the differences in their pharmacokinetic profiles whereby the short-acting formulations tend to improve post-prandial glucose effects by slowing gastric emptying and the long-acting formulations tend to have predominant effects on fasting-plasma glucose. 23,31 Consequently, the short-acting prandial GLP-1 receptor agonists are best suited to combination with basal insulin as either free standing or fixed dose agents, especially for patients who need to improve prandial glycemic excursions and who are concerned about weight gain and hypoglycemia. 7,8,21,23,27,28,29,35,36 Education is required to ensure physicians have the tools to reappraise anachronistic strategies for treating postprandial hyperglycemia in patients uncontrolled on basal insulin keeping in mind the updated 2015 ADA position statement, regimen safety and complexity and pharmacologic properties of the GLP-1RA 7,8,21, 23,28,36 class. Sanofi is seeking proposals to close the independently identified gaps for healthcare practitioners treating diabetes patients so that the unmet needs associated with appropriate basal insulin intensification and advancement of therapy can be addressed such that basal insulin patients unable to meet A1c goals, yet

2 meeting FPG targets receive therapeutic combinations with complementary mechanisms of action intended to manage post-prandial hyperglycemic excursions. The Endocrine Society announced the possibility of satellite symposia for accredited educational activities during their 2016 annual meeting and Sanofi will consider proposals including this and other venues. American College of Physicians announced the possibility of satellite symposia for accredited educational activities during their 2016 annual meeting and Sanofi will consider proposals including this and other venues. American Diabetes Association announced the possibility of satellite symposia for accredited educational activities during their 2015 annual meeting in Boston, MA (6/5-9th) and Sanofi will consider proposals including this and other venues. The American Association of Diabetes Educators has announced the possibility of satellite symposia for accredited educational activities during their 2016 annual meeting and Sanofi will consider proposals including this and other venues. MEDs has announced the possibility of satellite symposia for accredited educational activities during their 2016 annual meeting and Sanofi will consider proposals including this and other venues PriMed has announced the possibility of accredited educational activities during their regional conferences in 2016 and Sanofi will consider proposals including this and other venues. Web-based activities and chapter meetings will be considered that are aligned to the described educational gaps above. Preference will be given to proposals that include the unmet needs of patients requiring RAI therapy and the patient provider communications required to make the transition to a basal insulin intensification strategy. Preference will be given to proposals that recommend a format likely to enhance a practitioner s ability to manage hyperglycemia in patients on basal insulin currently unable to achieve A1c targets Preference will also be given to proposals that develop content customized to the different audiences attending Endo Soc, ADA, ACP, AADE, PriMed, MEDs, or other recommended meetings/ activities. Please note that proposals are expected to include the perspectives of patients in the analysis of the barriers and root causes for this gap and appropriately designed educational interventions. Proposal should include the following information: Needs Assessment/Gaps/Barriers: Include a comprehensive needs assessment that is well referenced and demonstrates an understanding of the specific gaps and barriers of the target audiences (i.e., ACCME accreditation element 2). The needs assessment must be independently developed and validated by the accredited provider Target Audience and Audience Generation: Proposal should describe the target audience(s) and provide a rational for how and why this target audience is important to closing the identified healthcare gap. In addition, please describe methods for reaching the target audience(s) including description of and rationale for recruitment and placement strategies to maximize participation according to need. Any unique recruitment efforts specific to the target audience should be highlighted. Learning Objectives and Content Accuracy: Provide clearly defined and measurable learning objectives framed as expected practice improvements in relation to the identified gaps and barriers. Include an overview of program content and explanation of criteria that will guide content selection, considering level of evidence and other variables. Sanofi-Aventis is committed to the highest standards in ensuring patient safety; the applicant should describe methods to ensure complete, accurate, evidence-based review of key

3 safety data for any therapeutic entities discussed in the activity. Explain how content will be updated if necessary throughout the program period, and how accuracy will be ensured. Educational Methods: The ACCME calls for educational methods that are clearly designed to address the knowledge, competence and/or performance gaps that may underlie an identified healthcare gap. Your proposal should demonstrate an understanding instructional design issues as they relate to the gaps in the knowledge, competence, or performance of the targeted audience. Education methods and design should be based on current literature in CME best practice and consistent with ACCME accreditation elements 3,4,5,6. For example, systematic reviews have suggested that the most effective continuing education is clearly linked to clinical practice, uses methods including interaction, reflection, strategies that ensure reinforcement through use of multiple educational interventions, and more. 38,39,40 Preference will be given to applications that utilize methods that have been shown to result in practice improvements, and/or with data on the effectiveness of other programs of the same type. ACCME criteria recognize that barriers may be related to systems, lack of resources, or tools etc. and these may be included if relevant in your discussion of the gap and the educational methods you propose. In addition, the educational preferences of the target audience(s) may be considered to maximize attendance/participation and lead to practice improvements. Faculty Recruitment and Development: Provide Information on the expected qualifications of contributors and description of methods to ensure recruitment of course directors and faculty who meet the qualifications. Explain any methods that will be used to ensure that faculty are fully trained in the program expectations and any skills that may be needed to ensure effective delivery of intended education. Program Evaluation and Outcomes: Provide a description of the approach to evaluate the reach and quality of program delivery; methods for monitoring individual activities and for ensuring ongoing quality improvements (Accreditation elements 12, 13, 14, 15). Describe methods that will be used to determine the extent to which the activity has served to close the identified healthcare gap. (Accreditation Elements 10, 11, 12), and the qualifications of those involved in the design and analysis of the outcomes. Preference will be given to programs with Objectives and Outcomes Plans of Moore level Budget: Include a detailed budget with rationale including breakdown of costs, clear explanation of the units, and calculations of: o Content cost per activity o Out-of-pocket cost per activity o Management cost per activity Accreditation: Programs must be accredited by the appropriate accrediting bodies and fully compliant with all ACCME criteria and Standards for Commercial Support TM. If you are a non-accredited provider, the accredited provider must be involved from the concept origin, fully knowledgeable of the grant submission and documentation should be provided on the website grant application section entitled, Other Information. Resolution of Conflict: The proposal should briefly describe methods for ensuring fair and balanced content, identification and resolution of conflict of interest, with particular emphasis on ACCME criteria 7, 8, 9. Communication and Publication Plan: Provide a description of how the provider will keep the supporter informed of progress. Include description of how the results of this educational intervention will be presented, published or disseminated.

4 References: 1. Centers for Disease Control and Prevention. National Diabetes Statistics Report. Estimates of Diabetes and Its Burden in the United States, Atlanta, GA: US Department of Health and Human Services; Inzucchi, S, Bergenstal, R, et al. Management of Hyperglycemia in Type 2 Diabetes: A Patient- Centered Approach. Diabetes Care 2015;38: Niswender, K. Early and aggressive initiation of insulin therapy for type 2 diabetes: what is the evidence. Clinical Diabetes 2009; 27(2): Hamaty, M. Insulin treatment for type 2 diabetes: when to start, which to use. Cleveland Clinic Journal of Medicine 2011; 78(6): Guigliano D et al. Efficacy of Insulin Analogs in Achieving the Hemoglobin A1c target of <7% in Type 2 Diabetes. Diabetes Care 2011; 34: Home, et al. Insulin Therapy in People with Type 2 Diabetes: Opportunities and Challenges. Diabetes Care 2014; 37: Perfetti, R. Combining basal insulin analogs with GLP-1 mimetics. Diabetes Technol Ther. 2011;13(9): Jendle, J, Martin, S. et al. Insulin and GLP-1 analog combinations in type 2 diabetes: a critical review. Expert Opinion. Posted online on July 16, (doi: / ). 9. Holman RR, Thorne KI, Farmer AJ, et al. Addition of biphasic, prandial, or basal insulin to oral therapy in type 2 diabetes. N Engl J Med. 2007;357: Buse JB, Bergenstal RM, Glass LC, et al. Use of twice-daily exenatide in basal insulin-treated patients with type 2 diabetes: a randomized, controlled trial. Ann Intern Med. 2011;154: Shah Br, et al. Diabetes patients with prior specialist care have better glycaemic control than those with prior primary care. J Eval Clin Pract 2005; 11: Home, P. et al. An observational non- interventional study of people with diabetes beginning or changed to insulin analogue therapy in non- Western countries. The A1chieve study. Diabetes Res Clin Pract 2011; 94: Rodbard, H, Jellinger PS, Davidson, JA et al. Statement by an American Association of Clinical Endocrinologists/American College of Endocrinology consensus panel on type 2 diabetes mellitus; an algorithm for glycemic control. Endocr Pract 2009;15: Leiter LA, Ceriello A, Davidson JA, et al. Postprandial glucose regulation: new data and new implications. Clin Ther. 2005;27[Suppl B]:S42-S Brunton S. Effective therapeutic options for managing postprandial glucose. J Fam Practice. 2008;57[Suppl]:S21-S Tenzer-Iglesias P and Brunton S. Managing postprandial glucose levels in patients with diabetes. J Fam Practice. 2008; 57[Suppl]:S17-S Monnier L, and Collete C. Targeting prandial hyperglycemia: how important is it and how best to do this? Curr Diab Rep. 2008(5): Woerle HJ et al. Impact of fasting and postprandial glycemia on overall glycemic control in type 2 diabetes: importance of post prandial glycemia to achieve target HbA1c levels. Diabetes Res Clin Pr. 2007; 77: Peyrot, et al. Insulin adherence behaviors and barriers in the multinational Global Attitudes of Patients and Physicians in Insulin Therapy study. Diabetes Med 2012; 29: Riddle, MD, et al. Individualizing targets and tactics for high-risk patients with type 2 diabetes: practical lessons from ACCORD and other cardiovascular trials. 21. Hirsch, I. et al. Options for prandial glucose management in Type 2 diabetes patients using basal insulin: addition of a short-acting GLP-1 analogue vs. progression to basal bolus. Diabetes Obesity and Metabolism 2013 doi: /dom Kendall DM, Cuddihy RM, Bergenstal RM. Clinical application of incretin-based therapy: therapeutic potential, patient selection and clinical use. The American Journal of Medicine 2009;122:S37-S Fineman MS, Cirincione BB, Maggs D, et al. GLP-1 based therapies: differential effects on fasting and postprandial glucose. Diabetes Obes Metab. 2012; DOI: /j x. 24. Eng C, Kramer CK, Zinman B, Retnakaran R (2014) Glucagon-like peptide-1 receptor agonist and basal insulin combination treatment for the management of type 2 diabetes: a systematic review and metaanalysis 25. Diamant M, Nauck MA, Shaginian R et al (2014) Glucagon-likepeptide 1 receptor agonist or bolus insulin with optimized basal insulin in type 2 diabetes. Diabetes Care 37: Balena R, Hensley IE, Miller S, Barnett AH (2013) Combination therapy with GLP-1 receptor agonists and basal insulin: a systematic review of the literature. Diabetes Obes Metab 15: Charbonnel B, Bertolini M, Tinahones FJ, Domingo MP, Davies M (2014) Lixisenatide plus basal insulin in patients with type 2 diabetes mellitus: a meta-analysis. J Diabetes Complicat 28:

5 28. Rosenstock,J et al. Advancing Basal Insulin Glargine with Prandial Lixisenatide QD vs. Insulin Glulisine QD or TID in T2DM: The GetGoal-Duo2 Evidence-Based Trial (NCT ). ADA 75 th Scientific Sessions Poster 107-LB. 29. Meier, J, Rosenstock, J. et al. Contrasting Effects of Lixisenatide and Liraglutide on Postprandial Glycemic Control, Gastric Emptying, and Safety Parameters in Patients With Type 2 Diabetes on Optimized Insulin Glargine With or Without Metformin: A Randomized, Open-Label Trial 30 Amori RE, Lau J, Pittas AG. Efficacy and safety of incretin therapy in type 2 diabetes: systematic review and meta-analysis. JAMA. 2007;298(2): Shyangdan, S. et al. Glucagon-like peptide analogues for Type 2 Diabetes Mellitus: systematic review and meta-analysis. BMC Endocrine Disorders 2010, 10: Khoo J, Rayner, CK, Jones KL, Horowitz, M. Incretin-based therapies: New treatments for type 2 diabetes in the millennium. Ther Clin Risk Manag. 2009; 5 (3): Garber, A. Novel incretin-based Agents and Practical Regimens to Meet Needs and Treatment Goals of Patients with Type 2 Diabetes Mellitus. JAOA 2011;111 (7); S20-S Nauck MA and Meier JJ. Pharmacotherapy: GLP-1 analogues and insulin: sound the wedding bells? Nat Rev Endocrinol. 2011;7: Meier JJ. GLP-1 receptor agonists for individualized treatment of type 2 diabetes mellitus. Nat Rev Endocrinol 2012; 8: Rosenstock et al. The benefits of fixed-ratio formulation of once daily insulin glargine/ lixisenatide (lixilan) versus glargine in type 2 diabetes patients inadequately controlled on metformin. Diabetes. 2014; 63 (Suppl 1) abstract 332-O. 37. Shaefer, C., Traylor, L. et al. Exploratory study of a dose response curve to basal insulin. Poster presented at 75 th Scientific Sessions of the ADA; 2015, June 5 th -9 th, Boston, MA 38. Davis D, Barnes BE, Fox R. (2003). The continuing professional development of physicians From research to practice; Chicago, IL: AMA. 39. Davis DA, Thomson MA, Oman D, et. al. (1999). Impact of formal continuing medical education Do conferences, workshops, rounds, and other traditional continuing education activities change physician behavior or health care outcomes? JAMA. 282: AHRQ. (2007). Effectiveness in continuing medical education. Evidence Report No Moore DE, Green JS, and Gallis HA. (2009) Achieving Desired Results and Improved Outcomes: Integrating Planning and Assessment Throughout Learning Activities. JCEHP, 29(1):1-15.