Presentation on theme: "Diabetes Management: a Regulatory view Luca Pani 10-11 giugno 2013."— Presentation transcript:
Diabetes Management: a Regulatory view Luca Pani DG@aifa.gov.itDG@aifa.gov.it 10-11 giugno 2013
Public Declaration of transparency/interests* Note: For this presentation I am not receiving any compensation *Luca Pani, in accordance with the Conflict of Interest Regulations approved by AIFA Board of Directors (26.01.2012) and published in the Italian Government Official Journal on 20.03.2012 according to 0044 EMA/513078/2010 on the handling of the conflicts of interest for scientific committee members and experts Interests in pharmaceutical industryNOCurrentlyLast 2 years More than 2 years but less than 5 years ago More than 5 years ago (optional) Direct interests: Employment with a companyX Consultancy for a companyX Strategic advisory role for a companyX Financial interestsX Ownership of a patentX Indirect interests: Principal investigatorX InvestigatorX Individual’s Institution/Organisation receives a grant or other funding X CME Courses X
Diabetes: not only a clinical problem Type 2 diabetes is the most common metabolic disease in Italy and in developed countries. It is the sixth leading chronic disease by diffusion with a crude prevalence of about 4.9%. It is estimated that about 3,500,000 Italians suffer from this pathology. The WHO estimates that every ten seconds a person dies for a disease related to diabetes
Incretin-based therapies The new class of Incretin-based therapies entered the arena, but their place in therapy remains difficult to determine because of limited long-term clinical data on both effectiveness and safety, and the high cost of therapy. Both GLP-1 receptor agonists and inhibitors of DPP-4 produce an improvement in glycemic control similar to other second-line therapies, but show some additional advantages with respect to weight gain and overall hypoglycemia.
Incretin-based therapies expenditure According to the OsMed report January-December 2012 on “The use of medicines in Italy”, the Incretin-based therapies expenditure is significantly increased.
Efficacy Incretin-based therapies have a innovative mechanism of action but they have not demonstrated a better efficacy than therapeutic alternatives, as shown by meta-analysis or clinical studies.
Safety In the clinical studies were reported ADRs including gastrointestinal symptoms (nausea, vomiting), hypoglycemia, increase of pancreatic enzymes and pancreatitis, rhinitis, nasopharyngitis and kidney damage.
International recommendations The main recommendation is to differentiate the target of HbA1c according to the characteristics of the patient (less stringent in the complex/fragile patient) and use the most appropriate hypoglycemic drug. Inzucchi SE et Al. Management of hyperglycaemia in type 2 diabetes: a patient-centered approach. Position statement of the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD). Diabetes Care. Vol 35. June 2012.
International recommendations Incretin-based therapies have not a better efficacy than therapeutic alternatives with a HbA1c reduction of about 0,5-1%. Inzucchi SE et Al. Management of hyperglycaemia in type 2 diabetes: a patient-centered approach. Position statement of the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD). Diabetes Care. Vol 35. June 2012. The appropriate use of Incretin-based therapy, in dual or triple therapy, concerns patients with a HbA1c level between 7.5% and 8.5%. In the complex/fragile patient a less stringent HbA1c level can be considered.
RCTs ≠ Real Life Data Real life data are essential to correctly assess the risk/benefit and benefit/cost ratio
Real life data concernig antidiabetic drugs The experience of AIFA Monitoring Registry Data collected by the AIFA Monitoring Registry from February 2008 to April 2012 concerned exenatide, sitagliptin, vildagliptin and, from 2010, saxagliptin and liraglutide. AIFA Monitoring Registry has the objective to monitor appropriateness of use, safety profile and effects on metabolic control.
Clinical and anthropometric baseline data 84,476 cases from the AIFA Antidiabetic Monitoring Registry were analyzed. DPP-4 inhibitors (saxagliptin, vildagliptin and sitagliptin associated or not with metformin) were prescribed in 47,566 cases and GLP-1 analogues were used in 36,910 cases.
Measures of therapeutic effect The mean change of HbA 1c ranged from -1.02 to -0.80%. The proportion of cases never reaching HbA 1c ≤7% ranged from 37.5% to 62.7%.
Total treatment costs and mean cost per patient The total economic NHS burden of cases selected from the Registry was 83,9 Million €: 42% for DPP-4 inhibitors and 58% for GLP-1 analogues. The daily mean cost per patient related to the drugs monitored in the Registry was around € 3.16.
Antidiabetics Italian NHS expenditure and consumption (DDD) data (2008-2012)
Real-world clinical practice AIFA Monitoring Registries have identified “niches” of inappropriate prescription of Incretin-based therapies considering the current national and international scientific evidence. Incretin-based therapies are a concrete example of the importance of evaluating a drug's efficacy and safety in real-world clinical practice in order to define the correct risk/benefit and benefit/cost profiles.
Reimbursement (without conditions) Refusal Outcome based MEAs Monitoring registers AIFA notes Therapeutic plans Payment by results Risk sharing Oncologicals Antidiabetics Psoriasis Orphans Cardiovascular Antireumatics Volume agreements Managing uncertainty relating to clinical benefit and cost-effectiveness Managing budget impact Managing utilisation to optimize performance Non-Outcome based MEAs Cost sharing Budget cap What are the AIFA's priorities? Supporting the prescription appropriateness and NHS sustainability considering the clinical evidence reported in the national and international guidelines and real life data.
Valorization of innovation AIFA’s new algorithm on innovation AIFA’s new domains Innovation must represent a therapeutic advantage Innovation must be "measurable“ on: Population selection. Robustness of endpoint(s). Choice of comparators. Duration of therapeutic effect Innovation should be valued against the National context Innovation must meet pharmaco-economic studies and HTA standards in order to determine the ratio of incremental cost-effectiveness compared to the standard reference standard
There is a need to compare the clinical trials data with the real life data to confirm the value of potential innovation. The AIFA Monitoring Registry provides the scientific community with the elements required to make choices targeted to the real needs of public health. The therapeutic effect of drugs monitored in the Italian real-world clinical practice in terms of HbA 1c mean reduction are similar to those recorded during phase 2-3 registration trials but with an high proportion of patients never reaching the clinical HbA 1c target suggesting the need to better characterize the subset of patients in which these treatments are effective. Data collected through the Registries are being used to evaluate the safety profile of Incretin based therapies which are today under closed scrutiny. Conclusions