IMPLEMENTATION OF ADAPTIVE CLINICAL TRIALS€¦ · Methodological Issues in Con˚rmatory Clinical...

IMPLEMENTATION OF ADAPTIVE CLINICAL TRIALSAn Aptiv Solutions White Paper

IMPLEMENTATION OF ADAPTIVE CLINICAL TRIALSIMPLEMENTATION OF ADAPTIVE CLINICAL TRIALS

PAGE 1 PAGE 10

ADAPTIVE CLINICAL TRIALS

Adaptive Clinical Trials (ACTs) dramatically improve the e�ciency of the clinical development process for both drugs and medical devices. ACTs rely on the timely collection of data in de�ned interim analysis steps providing the opportunity for the trial to adapt to emerging data (i.e. real time learning). For example, following an interim analysis, a decision may be made to re-estimate the sample size of the trial, stop the overall trial for futility, drop ine�ective treatments, or change the randomization allocation in favor of more e�ective treatments in de�ned sub-populations of patients. Importantly, these are not ad hoc changes but are design changes that are pre-speci�ed and planned in advance. Adaptive design concepts are applicable from Phase I to Phase IV. Regulatory agencies in US and Europe have published speci�c guidance documents on adaptive trials which support their use in exploratory Phase I to Phase IIb (“Learn”) trials and in adequate and well controlled Phase III (“Con�rm”) trials.

Although adaptive design concepts have been avail-able for some time, only recently has implementation (especially for complex design trials) been achievable. �is breakthrough has been possible because of the development of integrated technologies speci�cally designed to support the execution of ACTs. �e utilization of adaptive execution technologies along-side speci�c adaptive processes governing biostatistics, data management, project management and monitor-ing is opening up the potential for wider use of adaptive designs in clinical development. Importantly, these processes have to meet the requirements speci-�ed in draft agency guidance (e.g. FDA Draft Guid-ance for Industry: Adaptive Design Clinical Trials for Drugs and Biologics, 2010; EMA Re�ection Paper on Methodological Issues in Con�rmatory Clinical Trials Planned with an Adaptive Design, 2007).

�e essential requirements (Exhibit 1) for successful design, implementation and execution of ACTs are multi-fold:

• Expertise to develop innovative adaptive • methodologies including new validated design• software (e.g. ADDPLAN®, FACTS™)

• Expertise and experience in developing robust • solutions to address implementation challenges • Integrated technologies designed specifically to • manage the interim analysis steps central to the• adaptive trial process (e.g. AptivAdvantage™)

• SOPs, processes & work practices designed • speci�cally to support adaptive trial execution

ESSENTIAL REQUIREMENTS FOR SUCCESSFUL DESIGN AND IMPLEMENTATION OF ADAPTIVE CLINICAL TRIALS

EXHIBIT 1: The essential requirements for successful implementation of ACTs comprise (1) experts with specific experience in design and execution of adaptive trials, (2) integrated technology specifically designed for adaptive trial execution and (3) specific adaptive SOPs, processes, and working practices.

ADAPTIVE CLINICAL TRIAL EXECUTION

�e key to successful implementation of an adaptive design trial are processes that enable project manage-ment, data management and site monitoring to betailored to real time learning. �ese processes have to be integrated with systems that support electronic data capture, dynamic randomization, drug or device supply management (to minimize wastage), Data Monitoring Committee (DMC) structures, and operational �rewalls that ensure the validity and integrity of the trial.

ABOUT THE AUTHORS

COREY DUNHAM, SENIOR VICE PRESIDENT, GLOBAL DATA MANAGEMENT

Corey Dunham oversees global Data Management projects and activities at Aptiv Solutions, including oversight of the Data Technologies, Clinical Data Management and Data Entry functions. Mr Dunham serves as a senior member of the Aptiv Solutions technology team responsible for the growth and development of AptivAdvantage™. Mr Dunham will play a leadership role in helping clients understand the requirements for successful implementation of complex adaptive clinical trials. He also serves as a Consultant and Program Director for clients seeking to unify trial design with emerging technology. He has spent the last eleven years in the CRO industry working with innovative approaches to facilitate successful data collection. MARTIN GEUEKE, SENIOR VICE PRESIDENT, SOFTWARE DEVELOPMENT

Martin Geueke oversees the newly created Software Development group at Aptiv Solutions. Dr. Geueke is leading a global team dedicated to the development of new software to support adaptive clinical trial execution, including customized applications to support speci�c client requirements. Prior to this, Dr. Geueke led the European Data Management team at Aptiv Solutions. Dr. Geueke has over 16 years of experience in Clinical Data Management, Software Development and Information Technology. He has spent the past 12 years developing EDC systems, including iCRF, the proprietary EDC system developed by Aptiv Solutions and predecessor to AptivAdvantage™. JUDITH QUINLAN, SENIOR VICE PRESIDENT, ADAPTIVE TRIAL DESIGN AND IMPLEMENTATION

Judith Quinlan oversees the design and implementa-tion of adaptive clinical trials at Aptiv Solutions. Ms Quinlan previously worked at GSK for 10 years in both the UK and US. �roughout her time at GSK

Ms Quinlan worked as a strong advocate for adaptive designs. After leaving GSK four years ago, she joined the consulting industry. Ms Quinlan is an active member of the Adaptive Design Working Group (ADWG) where she has co-chaired the case study workstream that collected industry experience on the use of adaptive designs, the drug supply workstream, and currently co-chairs the monthly KOL lecture series on adaptive designs.

FURTHER INFORMATION AND ADVICE

Please email [email protected] for further information or to schedule a discussion with one of our adaptive design and implementation experts.

GLOSSARY

ACT Adaptive Clinical Trial

ADDPLAN® Adaptive Design: Plan and Analysis

CRA Clinical Research Associate

CTMS Clinical Trial Management System

DMC Data Monitoring Committee

eCRF Electronic Case Report form

3DES Triple Data Encryption Standard

EDC Electronic Data Capture

FACTS™ Fixed and Adaptive Clinical Trial Simulator

FDA Food and Drug Administration

IWRS Interactive Web Response System

SAE Serious Adverse Event

SDV Source Data Verification

sFTP Secure File Transfer Protocol

SOPs Standard Operating Procedures

to support those decisions must also be up-to-date, accessible and available at all times. Our interactive dashboards place this data in the decision makers’ hands in real time.

Aptiv Solutions believes in the world of automation and understands how both paper and manual processes in the collection of data can fall short due to transcription and �ling errors, not to mention time and resource consumption. Aptiv Solutions utilizes metrics in our clinical development programs to track study status, measure study progress and sta� performance. In addition, our metrics provide accu-rate predictions and likely outcomes on vital aspects of the clinical trial, such as enrollment and query collection, and whether or not we will meet our desired timelines given the current rate of progress.

CLIENT CUSTOMIZATION AND FURTHER TECHNOLOGY DEVELOPMENT AptivAdvantage™ has been developed by a dedicated team of very experienced software developers and aided by the operational experience of running over 100 adaptive trials for over a decade. �is team is responsible for developing and enhancing the corefunctionality of AptivAdvantage™ as well as implementing project speci�c requirements. In order to provide this programming support in an e�cientway, the software developers work very closely together with data management, project management, statisticians and the sponsor. Typical project speci�c implementations are related to data integration with external data providers or embedding of speci�c randomization procedures. �is approach ensures that customizations are implemented with high responsiveness.

Although a Help Desk system is available for ‘�rst-line’ support, the software development team is also responsible for provision of technical support during the course of the trial - from user support for site personnel to support for the clinical database programmers during the set-up process for the integrated IWRS and EDC system.

In terms of further development, the integration of AptivAdvantage™ with third party products will be continued, for instance to facilitate the automatic processing of SAEs by supporting the ICH E2B standard, and to provide robust links to a wider range of third party adaptive design engines.

INTEGRATION OF ADAPTIVE DESIGNS

�e approach that Aptiv Solutions takes to support adaptive trial execution has been to build an execution environment that operates with validated adaptive designs developed by Aptiv Solutions (ADDPLAN®) and other third party providers (e.g. FACTS™). Essentially this approach allows design engines to be easily plugged into the adaptive trial execution environment and therefore bene�t from the integrated functionality of AptivAdvantage™. As a consequence, AptivAdvantage™ provides a single integrated execu-tion platform for implementing the full range of adaptive designs required to cover all phases of clinical development. As new validated design methodologies become available, these will also be con�gured to interface with AptivAdvantage™.

THE APPLICATION OF APTIVADVANTAGE™ IN CONVENTIONAL TRIALS

Although AptivAdvantage™ has been developed speci�cally to support adaptive clinical trials, the integrated platform can also be used just as well in conventional trials as the integral processes associated with advanced project management, remote/central monitoring and drug supply management can also bring signi�cant e�ciencies to conventional studies as they do to adaptive studies.

�is white paper discusses these processes in more detail and focuses on technology solutions that enable e�ective implementation and execution of ACTs.

APTIVADVANTAGE™: THE INTEGRATED PLATFORM FOR ADAPTIVE TRIAL EXECUTION

AptivAdvantage™, the Aptiv Solutions Integrated Technology Platform, is at the heart of the data management process. �e platform has been created to limit the number of connection points and hand-o�s in the data collection process in order to provide a �exible and seamless environment that incorporates electronic data capture (EDC), randomization and drug supply management (Exhibit 2). It is a harmonization of technology, processes and people - all of which are key components of a successful adaptive trial. �e result is the facilitation of data-driven monitoring and real time data cleaning, which in turn enables timely database lock. �ese are critical features for the e�ective execution of adaptive trials and are speci�cally designed to meet regulatory agency requirements to minimize operational bias and maintain trial integrity.

THE DEVELOPMENT OF APTIVADVANTAGE™TRADITIONAL TRIAL CONFIGURATION

APTIVADVANTAGE™

EXHIBIT 2: AptivAdvantage™ is an integrated technology platform specifically designed for execution of ACTs. It incorporates EDC, randomization and drug supply management into a single database which has the ability to interface with validated adaptive design engines.

KEY SYSTEM FEATURES ELECTRONIC DATA CAPTURE (EDC)

AptivAdvantage™ is a cutting edge software platform where the system and processes are centered on the premise that data quality must be maintained at all times. As a result, the tools provided to the monitors and data managers are as robust as one would �nd in a traditional paper Clinical Data Management System. Is it also recognized that the user experience for the study coordinator and investigator is a key driver in ensuring the timely availability of clean data, and functionality to support these roles is also provided. �us the user interface is intuitive and designed to be easy to use, with help text and instruc-tions provided throughout the system. A key di�eren-tiation is the work�ow based dashboard portal (Exhibit 3), providing the user with a real-time view of their workload, any CRFs that need to be com-pleted and outstanding queries. �e dashboard facilitates productivity by guiding the user to the areas of most importance.

EDC SET-UP

A critical �rst step is the design of the electronic Case Report Form (eCRF), and the speci�cation of related

functionality, which need to be completed up front to ensure that all relevant clinical data is captured in a coherent manner. �is includes the creation of all code lists and the standards to be used for the clinical study under investigation. �is Functional Speci�cation is prepared by the Lead Data Manager and approved by the Sponsor and the Clinical Project Manager, and all customized reports and email noti�cations are de�ned within this speci�cation.

Based on the Functional Speci�cation, the Clinical Data Programmer creates the database and develops the necessary forms. Testing is completed, using two levels of testing procedures, to ensure all clinical data can be entered easily and correctly by the site. �e �rst testing procedure is performed within the Data Management department by a Clinical Data Manager who ensures the correctness of the programming

against all details given in the Functional Speci�cation document. After this internal testing, the Lead Data Manager initiates the release of the eCRF for User Acceptance Testing by the sponsor and trial site sta�, as necessary. User Acceptance Testing is completed to ensure that the work�ow for all roles is functioning as expected and continues until all functions perform as expected for each role. Once testing is completed, the eCRF is released for production.

THE INTEGRATION OF DATA MANAGEMENT AND STATISTICS

One of the major lessons gained from running over 100 adaptive trials has been recognition that “integration” is the major factor contributing to successful execution of such trials, not only at the level of IT, but also in terms of functional integration at

Principal Investigator has to learn two systems, IWRS to enroll the patient into the trial, and then the EDC system for data entry.

�e major bene�t to trial conduct is that it greatly reduces time consuming data exchange and the chance for information leakage, and alleviates misunderstandings between key trial participants.

Motivation Through Investigator Payments Linked to Data Entry

Principal Investigators are also motivated and trained to promptly enter data through payment by reward. From our experience this is an extremely successful motivational approach. Invoices and payments to investigators are automatically generated through AptivAdvantage™. �e set-up of this functionality is �exible and can be tailored to speci�c study needs. For example payment can be triggered by completion of data entry into the system, completed site veri�ca-tion of data, or even by % clean data. �rough this integrated system, investigators quickly learn that payment depends on timely data entry.

Study and site level payment reports are also auto-mated through the same system for Project Managers enabling them to track site performance. Automation of reports and payments increases e�ciency, site and Principal Investigator satisfaction and greatly reduces the burden on Project Managers, particularly for large multi-site trials. By alleviating this burden, Project Managers operate more e�ciently and have more time to concentrate on the interim analysis work�owprocess. In addition, the need for traditional site motivation by CRAs is also dramatically reduced which also adds to trial conduct e�ciency.

IN-STREAM DATA CLEANING

Ensuring that the appropriate amount of clean data is available for the interim analysis is critical to success for adaptive trials and as a consequence the data cleaning process and associated role speci�cations have been rede�ned.

In the traditional process where data cleaning is sequential and involves batch processing, moving data from EDC systems to data management systems, or to SAS programming, is ine�cient and not suitable for adaptive trials. Sequential processes create iterative data cleaning loops with signi�cant opportunity for transcription and other common data entry errors. Sequential approaches also slow the overall cleaning process and signi�cantly reduce the available time for the conduct of the interim analysis. Traditional batch cleaning is ine�cient due to delays in detecting data queries and failure to detect data queries early candramatically add to the overall cost of data manage-ment.

�rough use of the integrated processes controlled by AptivAdvantage™ study data is continually cleaned and reviewed in stream, and in parallel, by thecombined team e�orts of the data manager, program-mer, statistician and medical (physician) reviewer. �e goal is to clean all study data in stream during the trial, and not to simply focus on cleaning the primary data for decision making. Using this approach the time to database lock is dramatically reduced and in some cases database lock can occur within a few days of Last Patient Last Visit.

To help facilitate the cleaning process the data man-ager, statistician, programmer and medical reviewer are automatically noti�ed by the system if any changes occur, for example if new data is entered or existing data is updated. �e alert system is �exible and is tailored to speci�c study needs.

REPORTS & METRICS

For any service company to function optimally there needs to be ongoing measurement of the activities being performed and su�cient monitoring of the progress of studies being conducted. Technol-ogy is a vital component of this process in order to make sound and calculated strategies that are backed up by overwhelming evidence to support the decisions made. It is common practice in risk management for decisions to have to be made quickly and so the data

ADVANCED PROJECT MANAGEMENT & ADAPTIVE MONITORING

�e conduct of ACTs requires advanced trial management in which provision of fast, actionable performance metrics enable �exible project management. �e integrated technology platform is essential to enable continuous collection of informa-tion and transform this into actionable data, as is an experienced team that will make the information available to the right people at the right time.

�e continuous �ow of site performance metrics is a key element in the implementation of adaptive monitoring techniques and essential for remote monitoring. Real-time patient data provide continuous performance metrics giving operational teams clear visibility of how each site is performing, allowing them to schedule site visits based on site performance and study requirements.

�us, adaptive monitoring combines continuous remote monitoring with need-based site visits to optimize site performance and involves CRA time both in-house and on-site. �is replaces the �xed schedules and rigid adherence to prede�ned plans used in traditional studies, and allows dynamic resource allocation to all monitoring activities. To make this happen, the CRA has to encourage investigators to enter available data and to solve queries in a timely manner. �is assures that veri�ed and clean data are available in time for an interim analysis.

�e Project Manager ensures that all key elements necessary to perform an adaptive clinical trial are available on time:

• Integrated technology solution to manage the• interim analyses

• Training of team members (study-specific adaptive• customization)

• DMC member list

• DMC charter signed by all DMC members

• Signed contract with each DMC member

• Constitutional DMC meeting

• Training of site staff by CRAs

• Tracking of site performance during recruitment

• Statistical Analysis Plan for interim analysis

• Seamless trial continuation without any change, • stop or break

• Tracking of timelines for data availability

• Implementation of the DMC recommendation

A fully integrated technology platform reduces the manual e�ort required for Project Managers and CRAs to resolve queries, track patient visits and transfer information between systems and databases. It also ensures that all parties involved have complete visibility and control of the day-to-day functions of the trial.

PROMPT DATA ENTRY AT SITE

�e data cleaning process relies heavily on sites to promptly enter data, as the quicker data is entered, the sooner the data cleaning process can begin. �is is achieved through the following means:

Ease of Use for the Principal Investigator

�e bene�ts of AptivAdvantage™ to the Principal Investigator are that all interactions with regard to the study (patient enrolment and data entry) are under taken directly through a role-based portal into the web-based EDC component of the integrated platform. For example, to randomize a patient the investigator simply pushes a button in the integrated EDC system and subsequently logs onto the same EDC system to enter patient data. �e generation of randomization numbers and medication kit numbers are automatically linked, �rewalled and invisible to the investigator. For the investigator the experience is simple and conducted within a user-friendly environ-ment using only a single system which requires only a single password. When systems are not integrated the

the operational level. In this regard, IT systems, roles and processes have all been modi�ed and integrated in order to support the seamless execution of the interim analysis step central to the adaptive process.

For adaptive studies, data management, programming and statistics are no longer seen as separate functions that follow sequential processes. Within Aptiv Solutions, statisticians are responsible for specifying the amount of clean data for the interim analysis and are by role de�nition fully integrated into the study team during the conduct of a trial. �is integration ensures that all data needed for the interim analysis is available in time, which is critical for the success of the trial. In order to meet this requirement, study data is continually cleaned and reviewed in-stream, and in parallel, by the combined team e�orts of the data manager, programmer and medical (physician) reviewer. �is ongoing data review by a physician ensures that the data are medically plausible and in a state that is ready for interim analysis at all times.

�e goal is to clean all study data in-stream during the trial, and not to simply focus on cleaning the primary data for decision making. �is includes the coding of all relevant data as well as undertaking the SAE and external data reconciliations, resulting in data that areas clean as possible for making the correct adaptation decision.

RANDOMIZATION

AptivAdvantage™ delivers a truly interactive andweb based randomization which is completely embedded in the EDC component. Adaptive trials require robust yet �exible randomization engines that can adjust mid study (i.e. dropping a treatment arm or increasing a dose) or even dynamically as the data from previous patients dictate the next randomiza-tion. In order to execute these adaptations with the push of a button, sponsors require a robust and proven IWRS that is seamlessly integrated in real time with the EDC system. AptivAdvantage™ also o�ers a ‘statistician interface’ which enables even the most-complex randomizations to be developed, simulated

and validated all within the system. �is allows for quick deployment to the trial, and because it is utilizing the same database as the EDC system, AptivAdvantage™ reduces time to deployment by avoiding custom programming to integrate disparate systems (Exhibit 4). Any emergency unblinding during the course of the trial is supported by AptivAdvantage™ without any risk of unblinding stakeholders not involved in the process.

APTIVADVANTAGE™: INTERACTIVE WEB RANDOMIZATION

EXHIBIT 4: Through AptivAdvantage™ users can manage complex randomizations through the push of a button.

DRUG/DEVICE SUPPLY MANAGEMENT

Inventory control takes AptivAdvantage™ to the next level. In an adaptive trial with dynamic randomiza-tion, inventory control needs to be accessible to EDC at all times. �e system must know precisely what kits are on site and available for deployment. In the past, data technologists were required to facilitate this data exchange via nightly batch loads, sFTP exchange and, in the case of the ambitious, custom built Appli-cation Programming Interfaces. AptivAdvantage™ has eliminated all of this by creating an environment speci�cally for the product supply team which consti-tutes an interactive logistics, supply chain and inven-tory control management system (Exhibit 5). �is allows depot to depot exchange, supply packing and shipping to sites and a quarantine/stability interface with clinical supply and site. Investigators are also able to track shipments from within the EDC environment.

APTIVADVANTAGE™: DRUG SUPPLY MANAGEMENT

EXHIBIT 5: AptivAdvantage™ provides the product supply team with a fully integrated inventory control management system.

ADAPTIVE SOPS, PROCESSES AND WORKING PRACTICES

One of the key focus areas in maintaining the integrity of ACTs is ensuring that information is only made available to the appropriate trial participants. Regulatory agencies have a key concern on the protection, security and safeguards against the intro-duction of operational bias in adaptive trials. �e logistics of ensuring timely access to data at interim analyses gets more complex in adaptive trials. �is may involve the randomization schema, statistical analyses as well as logistics around drug supply. In addition to the normal participants in a clinical trial, the addition of interim analyses involves the inclusion in the work�ow of other groups, such as the Data Monitoring Committee (DMC). Aptiv Solutions has adhered to the following principles when developing their integrated IT platform, standard operating procedures (SOPs) and working practices for adaptive trials:

(1) To ensure maximum protection of the blind character of study data on all levels of data management, statistics, drug supply, and randomization (Exhibit 6)(2) To get clean data quickly under tight, well-de�ned deadlines (3) To undertake automated statistical analysis

(4) To control the communication �ow e.g. separation/independence of the DMC from the general trial activities, and (5) To transmit the recommendations of the DMC in a way that does not disclose these changes to members of the clinical trial team or Principal Investigators (Exhibit 7)

CRITICAL ROLE-BASED FUNCTIONAL INTERFACES

EXHIBIT 6: AptivAdvantage™ provides role-based functional interfaces with all operational teams responsible for trial execution and reporting.

THE CENTRAL ROLE OF APTIVADVANTAGE™ IN THE ADAPTIVE TRIAL PROCESS

EXHIBIT 7: AptivAdvantage™ sits at the heart of the adaptive interim analysis process and enables all of the adaptive procedures to be seamlessly implemented and managed

SOPS

A key starting point in the focus on maintaining trial integrity is the development of a defined set of SOPs. These SOPs govern the process of ‘who sees what and when’, and the work�ow to ensure that the correct data is delivered to the appropriate set of trial partici-pants. �e clinical trial protocol is the starting point, and it is critical that within this protocol only sum-mary data as to the process of adaption is contained. Explicit references to the entire processes to be followed in the adaptation will only serve to provide trial participants with knowledge as to subsequent

decisions by the DMC. Speci�c detail on the adapta-tion process should be included in documents with strict access controls. Contractual relationships with DMC members and other trial participants are also critical to ensure control of unauthorized information dissemination.

TECHNOLOGY FIREWALLS

Another key element is the set up and maintenance of technology �rewalls. �e integrated technology approach is aimed at providing e�ciency in execution through minimization of the number of handovers associated with data transfer. By minimizing handovers the risk of data leakage is reduced as is the risk of unintentional mistakes that may cause unblinding and jeopardize trial integrity. Firewalls in this context are de�ned as methodologies and processes to selectively protect information from being disseminated to unauthorized users. �is is not to be confused with the technical de�nition of �rewalls related to network architecture. Firewalls exist in AptivAdvantage™ between the randomization codes and the storage of other clinical data. �e randomization codes and the medication kit information are encrypted with the 3DES algorithm to prevent unintended access by administrative personnel. Access management within AptivAdvantage™ is controlled for all stakeholders via role-based permissions. Emergency unblinding is managed by the system in a unique way that ful�lls the highest standards in terms of data protection, accessibility, and documentation. Additional �rewalls are present in the way that documents are made available to DMC members and other trial participants. �e portals that make this data accessi-ble to the DMC members are role-based and pass-word protected. �is ensures that only the right data is made available to the right person at the right time. Moreover the system has full audit tracking and history log capabilities to verify at the end of the trial ‘who saw what and when’.

* While this document is written in the context of drug development all the basic operational principles apply equally to medical device development

TRIAL CONDUCT

INTEGRATEDTECHNOLOGY

PLATFORM

ADAPTIVE EXPERIENCE &DESIGN/IMPLEMENTATION

EXPERTISE

SOPs, processes & work practices designed specifically to support adaptive trial execution.

Integrated IT platform designed specifically to support adaptive trial execution e.g. AptivAdvantage™.

Adaptive methodology & design experts. Validated design software e.g. ADDPLAN®. Operational experience in conducting adaptive trials.


PAGE 9 PAGE 2












ABOUT THE AUTHORS








GLOSSARY





























APTIVADVANTAGE™




EDC SET-UP

















REPORTS & METRICS









• DMC member list


















RANDOMIZATION

















SOPS





EDC/RANDOMIZATION/DRUG SUPPLY/ADAPTIVE DESIGN ENGINEADAPTIVE INTEGRATED EXECUTION ENVIRONMENT

LABS IMAGING

EDC

CENTRAL DATA WAREHOUSE

LABS IMAGING

IxRS DRUG SUPPLY


PAGE 3 PAGE 8












ABOUT THE AUTHORS








GLOSSARY





























APTIVADVANTAGE™




EDC SET-UP

















REPORTS & METRICS









• DMC member list


















RANDOMIZATION

















SOPS





APTIVADVANTAGE™: FACILITATION OF RAPID AND ACCURATE TRIAL DECISION MAKING

EXHIBIT 3: Through AptivAdvantage™ users can access key trial data and metrics through a workflow-based dashboard portal providing users with a real-time view of their workload.


PAGE 7 PAGE 4












ABOUT THE AUTHORS








GLOSSARY





























APTIVADVANTAGE™




EDC SET-UP

















REPORTS & METRICS









• DMC member list


















RANDOMIZATION

















SOPS






PAGE 5 PAGE 6












ABOUT THE AUTHORS








GLOSSARY





























APTIVADVANTAGE™




EDC SET-UP

















REPORTS & METRICS









• DMC member list


















RANDOMIZATION

















SOPS





DATA ENTRY INTERFACE INVESTIGATOR ROLE

MONITORING INTERFACE

DATA MANAGEMENT QUERY INTERFACE

REPORTING INTERFACE

SPONSOR

DMC

DRUG/DEVICE

CRAs

STATS

MEDICAL

PM

DMCDMS

DRUGSUPPLY

RAND

STUDY DB

EDC/IWRS

EDC/IWRS

ISC

DMCPORTAL

INDEPENDENTSTATISTICIAN


PLATFORM

SYSTEMADMINISTRATOR

INDEPENDENTSTATISTICAL

CENTRE

SECUREPORTAL

DATAMONITORINGCOMMITTEE

PATIENT

SITES/PLsFIREWALLS

FIREWALLS


PAGE 7 PAGE 4












ABOUT THE AUTHORS








GLOSSARY





























APTIVADVANTAGE™




EDC SET-UP

















REPORTS & METRICS









• DMC member list


















RANDOMIZATION

















SOPS






PAGE 3 PAGE 8












ABOUT THE AUTHORS








GLOSSARY





























APTIVADVANTAGE™




EDC SET-UP

















REPORTS & METRICS









• DMC member list


















RANDOMIZATION

















SOPS





APTIVADVANTAGE™: FACILITATION OF RAPID AND ACCURATE TRIAL DECISION MAKING

EXHIBIT 3: Through AptivAdvantage™ users can access key trial data and metrics through a workflow-based dashboard portal providing users with a real-time view of their workload.


PAGE 9 PAGE 2












ABOUT THE AUTHORS








GLOSSARY





























APTIVADVANTAGE™




EDC SET-UP

















REPORTS & METRICS









• DMC member list


















RANDOMIZATION

















SOPS





EDC/RANDOMIZATION/DRUG SUPPLY/ADAPTIVE DESIGN ENGINEADAPTIVE INTEGRATED EXECUTION ENVIRONMENT

LABS IMAGING

EDC

CENTRAL DATA WAREHOUSE

LABS IMAGING

IxRS DRUG SUPPLY


PAGE 1 PAGE 10












ABOUT THE AUTHORS








GLOSSARY





























APTIVADVANTAGE™




EDC SET-UP

















REPORTS & METRICS









• DMC member list


















RANDOMIZATION

















SOPS





* While this document is written in the context of drug development all the basic operational principles apply equally to medical device development

TRIAL CONDUCT


PLATFORM

ADAPTIVE EXPERIENCE &DESIGN/IMPLEMENTATION

EXPERTISE

SOPs, processes & work practices designed specifically to support adaptive trial execution.

Integrated IT platform designed specifically to support adaptive trial execution e.g. AptivAdvantage™.

Adaptive methodology & design experts. Validated design software e.g. ADDPLAN®. Operational experience in conducting adaptive trials.

IMPLEMENTATION OF ADAPTIVE CLINICAL TRIALSAn Aptiv Solutions White Paper

IMPLEMENTATION OF ADAPTIVE CLINICAL TRIALS€¦ · Methodological Issues in Con˚rmatory Clinical...

Documents

Transcript of IMPLEMENTATION OF ADAPTIVE CLINICAL TRIALS€¦ · Methodological Issues in Con˚rmatory Clinical...