You are invited to submit an educational grant proposal to address the educational need(s) outlined in the attached document.

Transcription

1 Dear Sir or Madam: You are invited to submit an educational grant proposal to address the educational need(s) outlined in the attached document. Please note that Sanofi US has launched a new educational grant portal. Please submit proposal via the Sanofi US Educational Grant website at by 5p.m. EST on Wednesday October 12, Regrettably, if a submission is not submitted by this date, your proposal will not be accepted. When entering your proposal into the portal, please reference the following: RFP ID: Therapeutic Area: Area of Interest: Diabetes - New Complementary Insulin Combinations Diabetes New complementary insulin combinations to achieve HbA1c targets Please note that an applicant may be ineligible to receive educational grant funding in response to this RFP if the applicant or partners have performed any services under contract with Sanofi US during the last 12 months in connection with but not limited to the following in the same therapeutic area as this request for proposal (RFP): A consultant meeting; or An advisory board meeting If the applicant has performed such services, please forward a copy of the contract immediately, prior to responding to the RFP, so that we can determine your eligibility. If not, please acknowledge this in your application writing. Submission instructions are available on the website. If you have a content question, please contact Cindy Bocchino at Cynthia.Bocchino@sanofi.com. Regards, Theresa Glade Theresa Glade, Grant Coordinator, Contracted Position for Sanofi US IME Grant Operations Sanofi Diabetes and Cardiovascular 55 Corporate Drive Mailstop 55B 215A Bridgewater NJ Theresa.glade@sanofi.com Please consider the environment before printing this

2 Sanofi US Medical Affairs Request for Proposal Date: August 29th, 2016 Disease State: Diabetes Therapeutic Area: Diabetes Area of Interest: New complementary insulin combinations to achieve HbA1c targets Internal Requestor Information: Name: Cynthia Bocchino, BSN, RN Title: National Education Manager Phone: RFP ID: Diabetes New Complementary Insulin Combinations Due Date: no later than 5PM EST on October 12, 2016 Health Care Gap The Centers for Disease Control and Prevention estimates that 29.1 million Americans had diabetes in 2014 with type 2 diabetes accounting for % of those cases in adults. 1 Ensuing β cell decline predicts progression of hyperglycemia and requires timely optimization of treatment. 2,3 Hyperglycemia is the major factor responsible for both macrovascular and microvascular complications and every 1% reduction in HbA1c is associated with a 15% relative risk reduction in non-fatal MI and a 35% reduction in the risk of microvascular complications. 4,5,6,7,8,29 Despite declines in mean A1c values from 7.82% in to 7.18% in 2004, between 33.4 to 48.7% of patients with diabetes still do not meet targets for glycemia, blood pressure, and cholesterol control, and only 14.3% meet targets for the combination of all three measures. 9 The primary obstacles in maintaining HbA1c levels within the normal range remain progressive β cell failure and hypoglycemia. 10 Consequently, oral therapy is often insufficient for the maintenance of glycemic control and treatment intensification with insulin is generally required. 12 The current ADA/EASD position statement advocates sequential addition of anti-diabetes therapies with more established use and an emphasis on the individualization of care. 2,11 This treat to failure methodology has been criticized suggesting a more physiologic approach be instituted that also takes into account the 13,14 patients general health status and associated medical disorders. The physiologic approach seeks to correct specific glycemic disturbances by beginning with combination therapies known to have complementary mechanisms of action and subsequently correct the pathophysiologic defects in T2DM. 13,14 The EDICT trial suggests success in the physiologic approach to combination therapy in patients with newly diagnosed T2DM as compared to conventional sequential therapy, demonstrating better glycemic control with less hypoglycemia and weight loss, but this methodology represents a shift in current clinical practice. 14 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. 15,16,17,18 The underlying reason for poor glycemic control is often clinical inertia. In a retrospective cohort study of 80,000 T2DM patients, the median time to treatment intensification with basal insulin in patients inadequately controlled on oral anti-diabetic agents was 7.2 years with a median HbA1c of > 9.0%. In the same study, the median time to intensify patients with an HbA1c >7.5% using basal insulin was 4.3 years demonstrating a substantial proportion of patients remain in poor glycemic control for significant periods of time. 48 Barriers related to the introduction and intensification of insulin include fear of hypoglycemia, concerns about the injection procedure and need for multiple injections, anxiety about pain, and weight gain. 12,25 Progressive diminution of insulin secretory capacity for patients on basal insulin often leads to an additional requirement for prandial control. 2,19,20,21,22,23,24 The combination of a GLP-1RA and basal insulin have become well established after several studies confirmed improved glycemic control in the absence of weight gain and no increased risk of hypoglycemia in contrast to use of prandial insulin. 2,12,16,17, 28,30, 31,32,33,34,35,36,37,41,42,43,44 Real-world retrospective claims data however,

3 have demonstrated persistence with a free- combination of GLP-1RA and basal insulin to be low at 133 days, with only 17% persisting at 12 months. 49 While the GLP-1 receptor agonists share the same basic mechanisms of action, differences in their pharmacokinetic profiles result in differences in their effects on fasting and post-prandial glucose. Intermediate GLP-1RA exposure tends to slow gastric emptying thereby reducing post-prandial glucose excursions while continuous GLP-1 RA exposure down-regulates this effect and exerts predominant effects on fasting-plasma glucose. 32,38,39 Consequently, the short-acting GLP-1 receptor agonists may be best suited to combination with basal insulin as titratable fixed ratio combinations providing a complementary and additive effect to the individual agents. 12,16,17,28, 30,34,35,36,43, 44,45,46, 47 There is a clear need for education on the fixed-ratio combinations that will ascribe to the physiologic approach to therapy (FPG and PPG), hold promise in attenuating many of the barriers associated with basal insulin (e.g. weight gain, hypoglycemia, multiple daily injections) and GLP-1RA use (e.g. nausea, vomiting) and perhaps prompt improved adherence and drug persistence through a simplified treatment approach. 12,43,47 Sanofi US is seeking proposals to close these independently identified gaps for healthcare practitioners treating diabetes patients so that those patients unable to meet A1c goals may more effectively utilize titratable fixed-ratio combination therapies with complementary mechanisms of action to manage hyperglycemia, appropriately treat the physiologic defects of type 2 diabetes, minimize adverse events and perhaps improve persistence and adherence and assuage the barriers often associated with injectable therapies. The American Association of Clinical Endocrinology announced the possibility of satellite symposia for accredited educational activities during their 2017 annual meeting and Sanofi US will consider proposals including this and other venues. American College of Physicians announced the possibility of satellite symposia for accredited educational activities during their 2017 annual meeting and Sanofi US will consider proposals including this and other venues. American Pharmacists Association announced the possibility of satellite symposia for accredited educational activities during their 2017 annual meeting and Sanofi US will consider proposals including this and other venues. American Diabetes Association announced the possibility of satellite symposia for accredited educational activities during their 2017 annual meeting in Boston, MA (6/5-9th) and Sanofi US 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 2017 annual meeting and Sanofi US will consider proposals including this and other venues. AANP has announced the possibility of satellite symposia for accredited educational activities during their 2017 annual meeting and Sanofi US will consider proposals including this and other venues PriMed has announced the possibility of accredited educational activities during their regional conferences in 2017 and Sanofi US will consider proposals including this and other venues. Web-based activities and regional chapter meetings will be considered that are aligned to the described educational gaps above. Preference will be given to proposals that address barriers to OAD and insulin intensification and address the importance of effective patient provider communications. Preference will be given to proposals that recommend a format likely to enhance a practitioner s ability to manage hyperglycemia in the appropriate patients on OAD s and/or insulin and unable to achieve HbA1c targets

4 Preference will also be given to proposals that develop content customized to the different audiences attending AACE, 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. 54 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 rationale 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 US is committed to the highest standards in ensuring patient safety; the applicant should describe methods to ensure complete, accurate, evidence-based review of key safety and efficacy 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 criteria. 54 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 50, 51, 52 educational interventions, and more. 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. 54 Describe methods that will be used to determine the extent to which the activity has served to close the identified healthcare gap and the qualifications of those involved in the design and analysis of the outcomes. 54 Preference will be given to programs with Objectives and Outcomes Plans of Moore levels

5 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 nonaccredited provider, the accredited provider must be involved from the concept origin and fully knowledgeable of the grant submission. Resolution of Conflict: The proposal should briefly describe methods for ensuring fair and balanced content, identification and resolution of conflict of interest. 54 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. 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: DeFronzo, RA. Banting Lecture. From the triumvirate to the ominous octet: a new paradigm for the treatment of T2DM. Diabetes 2009; 58: Turnbull FM, Abraria C, et al. Intensive glucose control and macrovascular outcomes in Type 2 diabetes. Diabetologia 2009; 52: Erratum 52: The Diabetes Control and Complications Trial Research Group. The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus. N Eng J Med 1993: 329; UK Prospective Diabetes Study (UKPDS) Group. Intensive blood-glucose control with sulfonylureas or insulin compared with conventional treatment and risk of complication in patients with T2DM. (UKPDS 33). Lancet 1998: 352: Nakagami T. Kawahara R. et al. Glycemic control and prevention of retinopathy in Japanese NIDDM patients. A 10 year follow up study. Diabetes Care 1997; 20: Klein R., Klein BE, Moss SE. Relation of glycemic control to diabetic microvascular complications in diabetes mellitus. Ann Intern Med 1996; 124: American Diabetes Association. Standards of Medical Care in Diabetes Diabetes Care Volume 37, Supplement 1, January Seaquist, ER; Anderson, J. et al. Hypoglycemia and diabetes: a report of a workgroup of the American Diabetes Association and the Endocrine Society. Diabetes Care 2013; 36: DeFronzo, R, Eldor, R. et al. Pathophysiologic Approach to Therapy in Patients with Newly Diagnosed Type 2 DM. Diabetes Care, Volume 36, Supplement 2, August Del Prato S. Fixed-ratio combinations of basal insulin and GLP-1RA: is two better than one. Lancet; September 2, 2014, Pozzilli, P, Leslie, RD, et al. The A1c and ABCD of glycemia management in T2DM: A physicians personalized approach. Diaetes Metab Res Rev 2010; 26: Abdul-Ghani, M, Puckett, C. et al. Initial combination therapy with metformin, pioglitazone and exenatide is more effective than sequential add-on therapy in subjects with new-onset diabetes. Results from the Efficacy and Durability of Initial Combination Therapy for T2DM. Diabetes, Obesity and Metabolism 2015;17: 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: / 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:

6 19. 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: 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: Riddle, MD, et al. Individualizing targets and tactics for high-risk patients with type 2 diabetes: practical lessons from ACCORD and other cardiovascular trials. Diabetes Care 2012;35: 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 31. 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 meta-analysis. 32. 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: 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. 38. 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. 39. 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 millenium. 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 Diabets 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:

7 45. 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. 46. Rosenstock, et al. Prandial Options to Advance Basal Insulin Glargine Therapy: Testing Lixisenatide Plus Basal Insulin Versus Insulin Glulisine Either as Basal-Plus or Basal-Bolus in Type 2 Diabetes: The GetGoal Duo-2 Trial. Diabetes Care May; dc Rosenstock J, Aronson, R et al. Benefits of LixiLan, a Titratable Fixed-Ratio Combination of Insulin Glargine Plus Lixisenatide, Versus Insulin Glargine and Lixisenatide Mono-components in Type 2 Diabetes Inadequately Controlled With Oral Agents: The LixiLan-O Randomized Trial Diabetes Care 2016 Aug; dc Khunti, K, Wolden, M, et al. Clinical Inertia in People with T2DM. Diabetes Care 2013 Nov; 36(11): Fan, T, Linghor-Smith, et al. Real-world medication persistence and adherence associated with GI and GLP-1RA among patients with T2DM in the US. Poster presented at: AMCP Nexus, 2015; Orlando, Florida. 50. Davis D, Barnes BE, Fox R. (2003). The continuing professional development of physicians From research to practice; Chicago, IL: AMA. 51. 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): Accreditation Criteria. Accessed 26 August 2016.