EDC: THE EXPERIENCE OF A CRO

INTRODUCTION Expenditure on research and development by pharmaceutical industry is increasing worldwide and is currently estimated to be over $45 billion a year Despite the rise in R&D spending, there has not been a corresponding growth in the number of innovative drugs generated through such investment

INTRODUCTION One key bottleneck of turning biomedical innovations into actual product has been the design and execution of critical clinical trials to prove the safety and efficacy of various innovative biomedical products while balancing regulatory pressures with a constant drive to control costs and improve quality

INTRODUCTION It is widely believed that the adoption and use of information technology is critical in helping companies to satisfy these demands within the clinical operating environment

INTRODUCTION However, although technology dominates almost every aspect of our lives, from moving money safely, securely and predictably around the world without pen or signature to purchasing anything imaginable over the Internet……… in data collection from clinical trials “paper” is still king

INTRODUCTION Among the different technological solutions to be used in clinical trials, the “internet approach” offers the advantages of the combination of the desired targets in R&D: a) high quality b) shorter time c) lower costs

WHY THE INTERNET? Growing popularity/accessibility Many uses - business - personal - very low users barrier Still a number of concerns but progressively solved - privacy/security - data integrity - bandwith Integrating with other technologies

INTERNET APPLICATIONS FOR TODAY’S CLINICAL TRIAL Ethics submissions Patient recruitment Monitoring Patient education and communication Professional education (e-learning) Virtual Investigators’ meeting (video streaming) Electronic data capture Data Management

THE E-CLINICAL TECHNOLOGY MARKET Total spending in 2004 for external ECT solutions – hardware, software applications and implementation services – was an estimated $200 million. Presently, 15% of all newly initiated clinical trials are using e-clinical technologies suggesting a total potential ECT market of $1 billion to $1.3 billion if sponsors elect to use external vendor solutions

THE E-CLINICAL TECHNOLOGY MARKET The market is growing by 23% annually. Experts expect market growth to accellerate modestly due to the following key factors: FDA support for CDISC’s data submission standards has added credibility Investment capital continues to flow into the eClinical market at a significant level

THE E-CLINICAL TECHNOLOGY MARKET The market continues to consolidate as smaller players exit or are acquired Growing numbers of biopharmaceutical companies have been publicly reporting speed, quality and cost advantages in support of eCT solutions

THE E-CLINICAL TECHNOLOGY MARKET According to recent surveys, vendor solutions are offering improved functionality and performance Technology provisioning costs are dropping as adoption increases

WHAT INFORMATION EXISTS PROVING THE VALUE PROPOSITION OF EDC? The definition of value can be defined in: - direct economic (defined as pure cost-savings) - indirect economic (defined as opportunistic benefits such as the chance to increase revenue resulting from enhanced productivity) - societal implications (defined in this market as getting valuable drugs to market faster or preventing harmful drugs from being unduly exposed to patients)

WHAT INFORMATION EXISTS PROVING THE VALUE PROPOSITION OF EDC? The three most important criteria to improve in any product development effort are: Quality Time Cost

WHAT INFORMATION EXISTS PROVING THE VALUE PROPOSITION OF EDC? In market of drug and device development these factors are likely in the correct order and given the fact that approved products eventually sell for hundreds of million dollars annually, each of these factors have significant economic implications These three “metrics” have all been shown to be significantly impacted through the proper use of EDC

Comparison of metrics between EDC and paper methods in two Phase II clinical trials with the same drug and similarly sized projects ( by Banik, et al : Bayer Pharmaceuticals 1998)

ITEMIZATION OF EFFICIENCIES AND ADVANTAGES OF EDC OVER TRADITIONAL MANUAL METHODS

EDC vs PAPER: COST COMPARISON

EDC IN CLINICAL TRIALS : International experience AREAS OF COSTS SAVINGS The following are estimated cost eliminations of a 40 center, multicenter study with 1,000 patients and a 100 pages Case Report Form (CRF): Source: www.targethealth.com

EDC IN CLINICAL TRIALS : International experience AREAS OF COSTS SAVINGS Printing of the CRF: This cost can be as high as $100/book. For 1,000 patients, this represents a cost elimination of $100,000 plus resources to ship and direct shipping costs Source: www.targethealth.com

Double-Key Data Entry: EDC IN CLINICAL TRIALS : International experience AREAS OF COSTS SAVINGS Double-Key Data Entry: This cost can be as high as $3/pagex2. For a 100 page case book and 1,000 patients, this represents a cost elimination of $600,000 Source: www.targethealth.com

EDC IN CLINICAL TRIALS : International experience AREAS OF COSTS SAVINGS Query Management: In a case study comparing a paper query management system with an electronic online system using edit and logic checks, there was a 65% reduction in queries. For the current hypothetical study, there would be a reduction from 3,000 paper queries to approximately 1,000. Using an estimated in-house cost of query management of $50/query, there would be a savings of approximately $100,000 Source: www.targethealth.com

EDC IN CLINICAL TRIALS : International experience AREAS OF COSTS SAVINGS Monitoring: Since many monitoring problems can been identified in advance, there can be a reduction of at least one monitoring trip, as well as a reduction of time spent at the study site. Even if just one trip and an additional one day of monitoring is saved for each study site, for a multicenter study with 40 sites, the savings for one day of travel, one day of monitoring and travel costs could run up to $3,000/site.The total savings in this case would be $120,000 Source: www.targethealth.com

THE RISK OF EDC MISPERCEPTION The poor team workflow destroys the value proposition of EDC contributing to the misperception that “EDC is too expensive” In technology circles this is explained by the equation of New Technology + Old Process = Very Expensive Old Process (NT) (OP) (VEOP)

THE RISK OF EDC MISPERCEPTION

INTERNET APPLICATIONS FOR TOMORROW’S CLINICAL TRIAL THE “eCLINICAL TRIAL”

eCLINICAL TRIAL A clinical trial in which primarily electronic processes are used to collect (acquire), access, exchange and archive data and documents required for conduct, management, analysis and reporting of the trial

THE REAL BENEFITS OF AN eCLINICAL TRIAL APPROACH

THE REAL BENEFITS OF AN eCLINICAL TRIAL APPROACH Creating a more efficient and streamlined study management process and removing “paper” redundancies are indeed enormous measurable benefits

THE REAL BENEFITS OF AN eCLINICAL TRIAL APPROACH But there are other intangible benefits of eClinical trial that are not easily transparent and often difficult to measure which can be the most advantageous to the sponsor and CRO clinical study team

THE REAL BENEFITS OF AN eCLINICAL TRIAL APPROACH Dynamic site management Transparency Centralized study randomization Effective trial drug supply management Dynamic program management Better planning Less frequent site visits Shared documents file Continuous collaboration Real time safety evaluation Fast fail decisions

DYNAMIC SITE MANAGEMENT Problems with data quality captured at investigative sites, whether due to ineffective site training, poorly designed case report forms or inattentive site personnel, can be identified and resolved quickly, eliminating many errors downstream In a paper trial, repetitive errors build up over time because of the time lag between data entry and data validation/review.

DYNAMIC SITE MANAGEMENT In eClinical processes, automatic queries provide instantaneous corrective feedback to sites Clinical monitors have a continuous window into site data entry practices enabling them to intervene quickly before a small issues becomes a major problem

DYNAMIC SITE MANAGEMENT

DYNAMIC SITE MANAGEMENT

TRANSPARENCY One of the most overlooked benefits to an eClinical trial utilizing real time data capture and reporting is that the sponsor for the first time has the ability to measure their vendor’s (i.e. eCRO and participating sites) performance online in real time With information management tools, every site contact report, monitoring visit, and patient enrollment metric is available 24/7 from virtually anywhere in the world through an Internet connection

TRANSPARENCY

CENTRALIZED STUDY RANDOMIZATION The e-randomization procedure will prevent the incorrect enrollment, into the study, of patients not fulfilling all the inclusion and exclusion criteria. Therefore less patients are needed to reach the calculated sample size required for the per-protocol analysis Ultimately this will ensure reduced timelines and costs

CENTRALIZED STUDY RANDOMIZATION

EFFECTIVE TRIAL DRUG SUPPLY MANAGEMENT Assigning the randomization code and the appropriate “Trial Drug Kit”, the system automatically update the “Drug Distribution Process” and activate, if the case, the order of new supplies to investigational sites

EFFECTIVE TRIAL DRUG SUPPLY MANAGEMENT

EFFECTIVE TRIAL DRUG SUPPLY MANAGEMENT

DYNAMIC PROJECT MANAGEMENT Real time tracking of patient enrollment can help control trial size The continuous evaluation of screening results will help to determine whether protocol modifications may be required, such as inclusion/exclusion criteria

DYNAMIC PROJECT MANAGEMENT

BETTER PLANNING Earlier acces to better information allows to take an informed look at the next stages of the development program

LESS FREQUENT SITE VISITS In an eClinical trial environment, monitors review data inhouse between site visits. This ongoing review facilitates interaction/communication with site personnel and leads to dynamic site management Because ongoing data review is being performed, CRAs can visit sites less frequently saving on travel expenses as well

LESS FREQUENT SITE VISITS When visits are scheduled, actual monitoring time is used more efficiently and customized per site Surprises at the eClinical sites are virtually eliminated, and reducing CRA travel improves staff retention and productivity

LESS FREQUENT SITE VISITS

SHARE DOCUMENTS FILE eTrial Master File must be accessed by the CRO study team as well as by the Sponsor and the Investigators. Documents collection metrics (i.e. time to … or number of documents available etc) must be used as performance indicators for both CRAs and Investigators

SHARE DOCUMENTS FILE

CONTINUOUS COLLABORATION With eClinical trial, a study team is now unified by a common information set and the entire clinical team- sponsor, CRO and sites- can base decisions on accessible, real time, accurate information

REAL TIME SAFETY EVALUATION Because study data is received in real time, potential safety issues can be evaluated and appropriate courses of action determined quickly This allows for improved patient safety while also enabling quicker go-no go decisions based on safety issues that may arise

FAST FAIL DECISIONS With better and faster efficacy and safety information is possible to make more informed go-no go decisions

CONCLUDING COMMENTS As illustrated by the development of recruitment, electronic data capture, monitoring, patient education, project management, documents and data management applications, the Internet is becoming an inportant feature of today’s clinical trial paradigm

CONCLUDING COMMENTS cont’d For the Internet’s full potential of efficiency and quality improvement to be realized, there is a need for: - a more comprehensive appreciation of clinical trial activities (i.e. the eClinical approach with an integrated e-environment monitoring all the study related processes) - a commitment to data quality/regulatory requirements - universal attention to the development of standards (ICH/CDISC/HL7)

CONCLUDING COMMENTS cont’d The CRO must understand the value and benefits of the adoption of EDC technologies, and must be prepared to enforce effective new workflow in order to avoid the improper addition of tehcnology costs onto paper instead of logically eliminating redundancy

Thanks for your attention!