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Quantify hcv source and clinical outcomes database 0.0b

Quantitative Solutions and GVK Bio Confidential January 15, 2012 Quantify AD Clinical Outcomes Database
Release 2.0: January 15, 2012
1. Summary Information
The current version of the database includes clinical safety and efficacy information on all symptomatic drugs as well as newer AD drugs currently approved or in development for Alzheimer's Disease (AD). This document describes the structure and content of two databases, the source database and the clinical outcomes database. The source database is a database that maintains the sources of information identified by searches and reviewed for inclusion or exclusion from the database. The clinical outcomes database contains the information on trial, treatment and patients characteristics and safety and efficacy results of the trials identified for inclusion in the database
Table 1. Summary information
Parameter
Description
Alzheimer's Disease Last Updated
15-Nov-2011 Rivastigmine, galantamine, donepezil, memantine, tacrine, rosiglitazone, tramiprosate, AN1792, LY450139, PBT2, atorvastatin, celecoxib, dimebolin, naproxen, phenserine, rofecoxib, sertraline, simvastatin, tarenflurbil ADAS-cog, ADCS-ADL, CDR-sob, CGIC, CIBIS, CIBIC-plus, DAD, GDS, MMSE, sMMSE, NPI, NPI-CD, QOL-AD, PDS, responders, Key efficacy end points
SIB, Plasma/CSF levels of Abeta40 and Abeta42 Key safety end points
Tolerability percentages, dropout percentages Quantitative Solutions and GVK Bio Confidential January 15, 2012 2. Features and benefits
Key Features:
• Comprehensiveness: includes information for marketed drugs as well as drugs in
development; data source includes journal publications, conference posters, regulatory reviews, etc. • Ease of tracking: all clinical trial publications are listed in a separated source
database and linked to unique clinical trial names • Flexibility: the database design al ows for quick updates as wel as expansions to
include additional indications/drugs/endpoints/trials • Model-friendliness: designed and reviewed by experienced modelers to ensure
highest quality and usability for modeling and simulation to support drug development strategies • Customizability: can be augmented with clinical trial data proprietary to the
client (this information goes into a separate proprietary database and will be owned by the client)
Potential Applications:

Understand relative efficacy and safety profiles
This type of analysis is important and frequently done, especially for compounds in crowded
diseases. Population differences, design differences, and endpoint variability make direct
numbers difficult to compare. Clinical outcomes databases capture a broad range of trial-
specific information, which enables comparative efficacy and safety analysis NORMALIZED by
variants such as existing therapy, placebo response, patient characteristics, etc.
Link/Scale different endpoints or indications
Clinical outcomes databases aggregate endpoint data from tens of thousands of patients,
making it possible to make reasonable predictions of clinical outcomes from existing data. For
example, clinical teams find it valuable to predict a compound's performance in late phase
development based on early development biomarkers, or short-term efficacy studies.

Why use our databases:
• Designed and managed by experienced modelers • Provide most relevant data to support clients' needs for quantitative decision • Contain up-to-date and high quality data so that it is always readily available to provide timely analysis required to support critical clinical trial decisions • Supported by additional services such as modeling and simulation consulting services (by QS) and custom curation services (by GVK Bio) Quantitative Solutions and GVK Bio Confidential January 15, 2012
3. Organization and Structure
This product consists of two databases, the source database and the clinical outcomes database(core database). The source database is a database that maintains the sources of information identified by searches and reviewed for inclusion or exclusion from the database. The clinical outcomes database contains the information on trial, treatment and patients characteristics and safety and efficacy results of the trials identified for inclusion in the database. The fol owing is a flowchart showing the process with which databases are created, optimized and updated. • Define search criteria• Pubmed, regulatory websites, conferences • Update twice annual y • Tabulate al search results • Repeat the creative • Review / select references • Track inclusions/exclusions • Data exploration • Refine specifications • M&S to support drug • Curate data and QC • Develop documentation • Performance feedback • Incorporate M&S feedback 4. Overview of the Alzheimer's Source Database
The primary data sources were controlled clinical trials published in the medical
literature or available through FDA and EMEA. A secondary source of information was ClinicalTrials.gov, all trials for the treatments of interest were Quantitative Solutions and GVK Bio Confidential January 15, 2012 reviewed and data available on ClinicalStudyResults.org (http://www.clinicalstudyresults .org/) was evaluated. 581 references were identified and documented in the source database, of which a total of 136 were selected for inclusion in the database after careful review. The detailed reference information as well as reasons for exclusion is recorded to facilitate potential future expansion of the database. 5. Overview of the Alzheimer's Clinical Outcomes
Database
The clinical outcomes database contains information from 129 trials, representing 336
unique treatment arms and about 38,184 patients. There are a total of 8222 rows in the
database. Each row contains the information for an endpoint in one arm of a trial at a
specific point in time.
Table 2. Overview of trials in the AD database
# of trials
# of arms
# of patients
Quantitative Solutions and GVK Bio Confidential January 15, 2012
Table 3. Overview of efficacy endpoints in the AD database
# of trials
# of arms
# of patients
ADAS-cog <=-4 ADAS-cog <=-7 CGIC improvement CIBIC-plus improvement CIBIC-plus worsening Quantitative Solutions and GVK Bio Confidential January 15, 2012 6. Example Plots of data in the Alzheimer's Database
The fol owing graph shows examples of the time course of ADAS-cog as change from
baseline. The graphs show the time course for each treatment arm and each trial that has information on this endpoint. Quantitative Solutions and GVK Bio Confidential January 15, 2012 7. Outcome Fields
7.1.
Efficacy outcomes fields
The following efficacy measurements are recorded in the database • ADAS-cog: Alzheimer's Disease Assessment Scale – Cognitive Subscale total score — includes different responder definitions: much improvement, improved, no change, worse, much worse • CIBIS: Clinician's Interview-Based Impression of Severity • CIBIC-plus: Clinician's Interview-Based Impression of Change Plus Caregiver Input — includes different responder definitions: much improvement, improved, no change, worse, much worse • ADCS-ADL: the Alzheimer's Disease Cooperative Study Activities of Daily Living • CGIC: Clinical Global Impression of Change • MMSE: Mini-Mental State Examination • sMMSE: standardized Mini-Mental State Examination • NPI: Neuropsychiatric Inventory • NPI-CD: NPI-caregiver distress scale • SIB: Severe Impairment Battery • CDR-sob: Clinical Dementia Rating sum-of-boxes • QOL-AD: the quality of life-AD scale • DAD: Disability Assessment for Dementia • CBQ: Caregiver Burden Questionnaire • GDS: Global Deterioration scale • PDS: Progressive Deterioration Scale • FRS: Functional Rating Scale • IADL+: modified Instrumental Activities of Daily Living • MSMS+: modified Physical Self-Maintenance Scale • Plasma/CSF levels of A40 and A42 (Category is "A beta" for A ß40 and Aß42 levels and Category is "PK" for the Plasma drug concentrations) Quantitative Solutions and GVK Bio Confidential January 15, 2012 7.2.
Safety/tolerability Outcomes Fields
The fol owing safety and tolerability information is recorded in the database. The number of patients, percent of patients or rate (events per patient year) is recorded. For each safety outcome the numeric values (mean, etc) is also extracted if available at baseline or during trial: • Dropout: Total dropout/treatment discontinuation. This refers to al patients that did not complete the study or that did receive rescue therapy. In trials in which rescue treatment was provided also the dropout minus the patients that receive rescue is provided (dropout – rescue) • Dropout AE: Dropout related to adverse events • Dropout Efficacy: Dropout related to lack of Efficacy. Some trials provide rescue therapy for patients with lack of efficacy. The number of patients that rescue is captured from those trials. This can be compared to dropout due to lack of efficacy. • Rescue: Patients receiving rescue treatment due to lack of efficacy (Category is • Death • AE total: any adverse events • AE clinical: clinical adverse events • AE lab: laboratory adverse events • AE serious: serious or severe adverse event • dose increase, interruption, reduction or modification: AE resulting in changes in • nausea • vomiting • dizziness • diarrhea • headache • somnolence • accidental/inflicted injury • abdominal pain • anorexia • depression • agitation • infection upper respiratory: upper respiratory infection Quantitative Solutions and GVK Bio Confidential January 15, 2012 • infection urinary tract: urinary tract infection • insomnia • confusional state • hypertension • fatigue • rhinitis • muscle cramps • development of anti-drug antibodies

Source: http://quantitativesolutions.net/publications/Quantify%20AD%20information%20Sheet_021512.pdf