Barhi chf registry

T2DM REGISTRY PROTOCOL 2013
TITLE: A prospective, multi-centric, registry to describe pharmaceutical treatment patterns in
Indian T2DM patients starting on oral hypoglycaemic agents (OHA).
PROTOCOL NUMBER:
VERSION NO:
PROTOCOL VERSION DATE:
Dr. Siddharth N. ShahHon. Editor, Journal of Association of Physicians of India,Turf Estate, #6 & 7, Ground Floor, Opp. Shakti Mil s Compound, Dr. E. Moses Road, Opp. Mahalaxmi Station (West), Mumbai 400 011Tel. : (022) 66663224, 24912218 • Tel./Fax : 2492 0263 Journal of Association of Physicians of India,Turf Estate, #6 & 7, Ground Floor, Opp. Shakti Mil s Compound, Dr. E. Moses Road, Opp. Mahalaxmi Station (West), Mumbai 400 011Tel. : (022) 66663224, 24912218 • Tel./Fax : 2492 0263 Information contained in this protocol is confidential in nature, and are protected by the confidentiality agreement and Financial Disclosure Agreement signed prior to releasing of this document. The contents of this document may not be used, divulged, published or otherwise disclosed to others except to the extent necessary to obtain approval of the Institutional Review Board or Ethics Committee, or as required by law. Persons to whom this information is disclosed should be informed that this information is confidential and may not be further disclosed without the express permission of JAPI. All intellectual properties arising out of this study belongs to the Sponsor.
T2DM REGISTRY PROTOCOL 2013
Table of Contents

T2DM REGISTRY PROTOCOL 2013
1. Synopsis
A prospective, multi-centric, registry to describe pharmaceutical treatment patterns in Indian T2DM patients starting on oral hypoglycaemic agents (OHA).
Type 2 diabetes mel itus patients who are prescribed a new OHA, irrespective of prior therapies, as part of a physician’s therapeutic intervention and discretion. The new OHA prescribed could be a first monotherapy, a change in monotherapy, or an add-on second line or third line therapy.
Contraindications to metformin and OHA’s according to the Summary of Product Characteristics/Prescribing information.
Metformin alone or in combination with OHA’s, insulin, GLP-1 analogues at the physician’s discretion on prescription. To describe the pharmaceutical prescription pattern in Indian T2DM Primary End Proportion of patients starting on various OHA’s point 1. To compare Indian prescription pattern with international guidelines (1st line therapy with lifestyle modifications) 2. To correlate the pharmaceutical intervention with demographic and clinical characteristics of the Indian T2DM population 3. To understand the initiation, titration and maximum dose of 4. To understand whether metformin, when initiated, is as monotherapy or in combination with other anti-diabetic agents.
1. Proportion of patients starting OHA’s who are treated according to T2DM REGISTRY PROTOCOL 2013
2. Correlation of pharmaceutical intervention with demographic and clinical characteristics of the Indian T2DM population 3. Proportion of patients started on the different metformin-based therapies, i.e. as monotherapy or in combination with other antidiabetic agents 4. Proportion of patients started on the respective doses of metformin for each of the metformin-based therapies 5. Initiation and maximum doses (mean, median, range) of metformin 6. Incremental/decremental metform dose (mean, median, range) during titration as monotherapy and in combination 7. Change in fasting blood glucose and HbA1c after 3, 6 and 12 months on various treatment regimens including metformin as monotherapy and in combination Being a registry, only descriptive statistics wil be applied. To ensure a comprehensive representation of the Indian population, the target is to col ect data from a minimum of 10,000 patients.       T2DM REGISTRY PROTOCOL 2013
2. Background:
RationaleIncreasing Burden of Diabetes in India
In Indians, Diabetes is emerging as one of the important causes of mortality & morbidity. The global estimated mortality for diabetes in 2005 was 1.1 mil ion. This quoted figure is considered an underestimate as diabetes rarely features as the primary cause of death in death certificates. The international diabetes federation estimates that the number of diabetic patients in India has more than doubled from 19 mil ion to 40.9 mil ion from 1995 to 2007. It is projected to increase to 60.9 mil ions by 202 The WHO estimates that the mortality due to diabetes and/or heart disease costs India more than $210 mil ion. Over the period of the next 10 years this cost is projected to increase to more than $335 mil io Sparse Indian clinical (epidemiology / treatment trends / diabetic complications) data.
Despite the large number of patients, research and/or data on diabetes in India is very scanty. Although India houses more than 17% of the global diabetic patients, only 2% of research published on pubmed is dedicated to diabetic Indians. Moreover, this data is obtained from discrete studies; there is a significant lack of pan-India data. There is a lack of standardized care for the diabetic patients in India. Treatment differs from the endocrinologist to consulting physician and again to general practitioner. In addition, there is vast difference between urban and rural patient care. Metformin is recommended as the first line antidiabetic agent in most of the international guidelines (IDF, EASD, ADA). Therefore it is our endeavour to partner with the local KOLs and local professional bodies to col ect daily practice data on T2DM as wel as its management in the form of registry. The data col ected wil be compared with International recommendations.
Research Questions
The registry would col ect epidemiological, clinical and treatment data of patients in daily practice who are starting OHA. The data col ected are aimed at addressing the fol owing questions regarding the prescribing patterns of physicians in India: a. Is the pharmaceutical intervention strategy based on certain patient profile such as: • Demographic profiling• Clinical profiling• Anthropometric profiling of patients • Complication related profiling b. When in the course of diabetes and how is metformin and other OHA’s prescribed? T2DM REGISTRY PROTOCOL 2013
• duration of diabetes when metformin and/or other OHA’s is prescribed• as 1st line or 2nd line • whether in association with diet and lifestyle changes• metformin prescribed alone or in combination with other agents c. What is the fol owing dose of metformin as monotherapy and in combination with other • Dose at initiation of metformin• Incremental/decremental dose change during titration• Maximum dose of metformin achieved i. World Health Organization. Fact sheets available from http://www.who.int/mediacentre/factsheets/fs312/en/ ii. Secree R, Shaw J, Zimmet P. “Diabetes and Impaired glucose tolerance” In Gan D (editor): Diabetes atlas: International Diabetes Federation; 3rd edition, Belgium: International Diabetes Federation; 2006: 15-103 3. Study Objectives
Primary Objective:
• To describe the pharmaceutical prescription pattern in Indian T2DM patients starting on Secondary Objectives:
• To compare Indian prescription pattern with international guidelines (1st line therapy • To correlate the pharmaceutical intervention with demographic and clinical characteristics of the Indian T2DM population • To understand the initiation, titration and maximum dose of metformin prescribed.
• To understand whether metformin, when initiated, is as monotherapy or in combination There can be further multiple secondary end points that can be evaluated in further subgroup analysis. T2DM REGISTRY PROTOCOL 2013
4. Study Design
The T2DM Registry is designed as a multicenter clinical database on the patient characteristics
and therapeutic management and outcomes of patients treated for T2DM. Each site wil have
an Ethics Committee approval; if EC is not available at the site selected – approval from
Independent Ethics Committee wil be obtained. Each patient wil be explained the relevance of
the data col ection and an Informed Consent Form wil be signed by the patient. There wil be
NO additional tests/procedures undertaken for the purpose of registry data and T2DM registry
would be a completely an observational registry. There will be no protocol specific changes as
far as patient care is concerned. No predefined investigations and treatment are suggested.
Data wil be captured by predesigned case record forms. Some center wil be considered as coordinating centre for data processing purposes. Similarly, some investigators wil be appointed as the Coordinating Investigators and wil be responsible for the Coordination and helping other sites and data entry process. The data management team wil be responsible for data entry and accuracy of data.
5. Study Patients
Inclusion Criteria
Type 2 diabetes mel itus patients who are prescribed a new OHA, irrespective of prior therapies, as part of a physician’s therapeutic intervention and discretion. The new OHA prescribed could be a first monotherapy, a change in monotherapy, or an add-on second line or third line therapy.
Exclusion Criteria
Contraindications to metformin and OHA’s according to the Summary of Product Characteristics/Prescribing information.
6. Materials
The investigator wil be supplied with the fol owing materials for initiation and conduction of the study.
T2DM REGISTRY PROTOCOL 2013
7. Drugs
Anti-diabetic drugs wil be prescribed at the discretion of the physicians. The drugs could
include al OHA’s (including metformin) and injections such as insulin and GLP-1 analogues.
Any concomitant treatment given to / taken by the patient must be recorded in the case report form.
8. Visits
The registry would capture data over 4 visits. The first visit (baseline) is when the patient visits for a medial consultation. This wil be fol owed by 3 fol ow-up visits at the end of 3, 6 and 12 months. 9. Assessment
Primary endpoint
• Proportion of patients starting on various OHA’s Secondary endpoint
T2DM REGISTRY PROTOCOL 2013
• Proportion of patients starting OHA’s who are treated according to international o The percentage of patients on different OHA would be identified. It would be studied whether this reflects prescription pattern that meets the directions given in various international guidelines (e.g. American Diabetes Association, European Association for the Study of Diabetes) in terms of the drug of first choice and of the subsequent selection of drug of second and third choice. The duration before which insulin therapy is added to the OHA regime wil also be studied. The trend by which patients are selected for a particular treatment wil be evaluated • Correlation of pharmaceutical intervention with demographic and clinical characteristics o The correlation between the choice of OHA and demographic parameters like age, gender, BMI, diet, smoking, occupation, physical activities, and alcohol consumption wil be studied. The correlation between the choice of OHA and clinical characteristics like duration of onset of diabetes, complications of diabetes, Blood sugar levels, HbA1c, etc, wil also be evaluated. • Proportion of patients started on the different metformin-based therapies, i.e. as monotherapy or in combination with other antidiabetic agents o The correlation between the choice of OHA and demographic parameters like the age, gender, BMI, diet, smoking, occupation, physical activities, and alcohol consumption would be determined. The correlation between the choice of OHA and clinical characteristics like duration of onset of diabetes, complications of diabetes, Blood sugar levels, HbA1c, etc, would be evaluated. • Proportion of patients started on the respective doses of metformin for each of the • Initiation and maximum doses (mean, median, range) of metformin as monotherapy o Proportion of patients on minimum and maximum dose would be determined.
• Incremental/decremental metform dose (mean, median, range) during titration as T2DM REGISTRY PROTOCOL 2013
• Change in fasting blood glucose and HbA1c after 3, 6 and 12 months from baseline on various treatment regimens including metformin as monotherapy and in combination o The efficacy of various treatment regimens including metformin as monotherapy and in combination wil be determined by evaluating the change in fasting blood glucose and HbA1c after 3, 6 or 12 months of therapy. 10. Data col ection
Prospective data col ection wil be done during al the visits at baseline, and at the end of 3, 6
and 12 months. The fol owing data wil be captured.
• Month and year of diagnosis.
• Time of initiation of first line treatment from the date of diagnosis.
• Treatment setting, i.e. GP, consultant physician, endocrinologist/diabetologist,
• Demography – Identification details, date of birth and gender.
• Clinical Characteristic
Fasting blood sugar OR
2- hour Post-Prandial Blood sugar OR
- Glycosylated Hemoglobin - HbA1c (%)- Other if available, e.g OGTT - Systolic Blood Pressure- Diastolic Blood Pressure - Concomitant diseases- Diabetic complications - • Dose
- Dose of metformin and OHA’s at initiation T2DM REGISTRY PROTOCOL 2013
Maximum titrated dose. This wil be taken as the maximum dose of metformin and OHA’s prescribed over the 12-month period, either as monotherapy or in combination - Metformin prescribed as fixed dose or free dose combination 11.Statistical analysis and Sample Size Estimation
Being a registry, only descriptive statistics wil be applied. To ensure a comprehensive
representation of the Indian population, the target is to col ect data from a minimum of 10,000
patients.    
  
12. Data Management
Data wil be entered in electronic case record forms (eCRFs). 13. Reporting and management of adverse events
An adverse event (AE) is any untoward medical occurrence in a subject or clinical investigation subject administered a pharmaceutical product, which does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporal y associated with the use of a medicinal product, whether or not considered related to the medicinal product. Investigators must assess the severity/intensity of adverse events according to the Qualitative Toxicity Scale as fol ows: • Mild: The subject is aware of the event or symptom, but the event or symptom is The subject experiences sufficient discomfort to interfere with or reduce Significant impairment of functioning: the subject is unable to carry out Investigators must also systematical y assess the causal relationship of AEs to Merck Product
using the fol owing definitions. Decisive factors for the assessment of causal relationship of an
AE to the treatments include, but may not be limited to, temporal relationship between the AE and the treatments; known side effects of treatments; concomitant medication, course of the underlying disease or impact of other treatment.
Serious Adverse Event
A serious adverse event (SAE) is any untoward medical occurrence that at any dose:
 Results in death.
T2DM REGISTRY PROTOCOL 2013
 Is life-threatening.
NOTE: The term “life-threatening” in this definition refers to an event in which the subject is at risk of death at the time of the event; it does not refer to an event that hypothetical y might cause death if it were more severe.
 Requires inpatient hospitalization or prolongation of existing hospitalization.
 Results in persistent or significant disability/incapacity.
 Is a congenital anomaly/birth defect.
 Is otherwise considered as medical y important.
Important medical events that may not result in death, be life-threatening, or require hospitalization may be considered as SAEs when, based upon appropriate medical judgment, they may jeopardize the subject or may require medical or surgical intervention to prevent one of the outcomes listed in this definition. Examples of such events include al ergic bronchospasm requiring intensive treatment in an emergency room or at home, blood dyscrasias or convulsions that do not result in inpatient hospitalization.
Events that Do Not Meet the Definition of an SAE
Elective hospitalizations to simplify study treatment or study procedures are not considered an SAE. However, al events leading to unplanned hospitalizations or unplanned prolongation of an elective hospitalization must be documented and reported as SAEs.
Al the adverse events in a patient administered Merck product should be considered and
treated as spontaneous. The investigator should inform Merck of the same and wil be handled
by the drug safety department based in Mumbai, Head Office. Serious adverse events occurring
during the registry period must be monitored and fol owed up by the Investigator until
stabilization or until the outcome is known, unless the subject is lost to fol ow-up. The
Investigator wil ensure any necessary additional therapeutic measures and fol ow-up
procedures. The serious adverse events for Merck related products should be fil ed in Merck
Adverse Events form provided along with and should be reported within 24 hours to local drug
safety officer / medical responsible person.
Safety reporting for drugs other than Merck products would be carried out by fil ing the Suspected Adverse Drug Reaction Reporting Form provided by local regulatory body - Central Drugs Standard Control Organization (CDSCO) and Investigator would forward the same to the Regional Pharmacovigilance centres (These centres are a part of the National Pharmacovigilance Center, India) as required by the local ADR reporting guidelines. A photocopy of the same would be attached to the CRF.
Drug Safety Officer : Sweta LopesPh No :022 66609030 T2DM REGISTRY PROTOCOL 2013
Deputy Drug Safety Officer: Ms. Aparna MirashiTel: + 91-22-66609064Mobile No: +91-9769721208 Address: Merck India Ltd; Shiv Sagar Estate –A, Dr. Annie Besant Road, Worli, Mumbai, India – 400018.
14. Data Archiving
The investigator wil retain al source document and the Informed consent documents in accordance with the local regulation. The investigator is recommended to contact the sponsor before disposing of any study records. The study related documents should be maintained by the sites for 5 years and should be made available for audit / inspection at any time, if required by regulators.
15. Study Reports
The study and its reports wil remain as properties of the sponsor, and the sponsors are free to publish the study results anywhere. The investigator (s) are also be free to publish their results but it is expected that any publication wil , as a matter of courtesy, be submitted to the sponsor for review and comment sufficiently early to al ow consideration of such comment by the investigator (s) prior to publication.
16. Publication Policy
The data captured in the registry wil be analyzed and reports wil be generated during the
discourse of registry. For making this report available to the medical community at large the
investigators wil try to publish the results in a peer reviewed widely circulated journal.
Although investigator wil be al owed to present his/her own data in various scientific meetings,
if they require other center`s data – they can avail that after approval of concerned doctors
with due credit given to their contribution. He/she cannot publish others data without
intimating and discussing with al the concerned parties including Merck Serono.
17. Quality Assurance
In compliance with regulatory requirements, the Sponsor, a third party on behalf of the
Sponsor, regulatory agencies, or IRB/IECs may conduct quality assurance audits / inspections at
any time during or fol owing a study. The Investigator must agree to al ow auditors/inspectors
T2DM REGISTRY PROTOCOL 2013
direct access to al study-related documents, including source documents, and must agree to al ocate his or her time and the time of his or her study staff to the auditors/inspectors in order to discuss findings and issues. The protocol, each step of the data capture procedure, and the handling of the data, as wel as the eventual study report, wil be subject to independent Clinical Quality Assurance. Audits may be conducted at any time during or after the study to ensure the validity and integrity of the study data.
18. Instructions to clinical Investigator
- Please read the protocol completely and carefully to be in total compliance.
- Select the patients who meet the inclusion & exclusion criteria.
- Explain in simple language the pros and cons of the study to the patients and confirm his Enrol the patient in the registry after obtaining written informed consent.
There wil be NO additional tests/procedures undertaken for the purpose of col ecting these registry data - There wil be no protocol specific changes as far as patient care is concerned. - No predefined investigations and treatment are suggested. - Enter al the required data in the Case Record Form during each patient visit.
- Record adverse effects, if any, in the case record form 19. Investigator’s Consent / Agreement
I have read the protocol MRCK/T2DM/REG/03/12/2011, Version 2, dated 4th December 2012
and I agree to conduct the study as described in it, and I compliance with ICMR guidelines, ICH-
GCP, the Declaration of Helsinki, and the rules and regulation of this country in force at present.
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