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PharPoint Video Series: Choosing an EDC Provider

 

Intimidated by the daunting task of choosing an EDC? Not sure what factors to consider? Find out about how to select the best EDC for your project with PharPoint Principal Data Manager Jenifer Ehlers.

  • Choosing an EDC Transcript

    “Whether choosing your first electronic data capture system, also known as EDC, or adding a new EDC platform to your arsenal, deciding between the numerous providers can be overwhelming.

    Many EDC providers can meet the basic needs for a study (regulatory compliance, the ability to enter data and make changes to it and the ability to export data from the system), but from there it’s like comparing apples to apples. Will a Red Delicious meet your needs or is a Honeycrisp a better fit? Just because a system has more to offer, doesn’t make it the best system for your company.

    To narrow your choices, you will want to consider costs, timelines, available features of each system, and the resources needed to support the study design with the EDC system, i.e.:

    • Do you have programming support for the system internally?
    • Will you need to outsource the service or can the EDC provider develop the study database for you?

    Breaking down the selection and implementation process into four stages will help your team choose the best system for your company’s needs without seeming like an impossible task.

    Stage 1: Identify the EDC Selection/Implementation Team and Set Expectations

    An ideal selection team will incorporate a mix of end users, such as:
    • Data managers
    • Monitors
    • Clinical support staff
    • Project managers
    • Statisticians
    • Programmers
    • Or representatives from QA

    Your selection team often evolves throughout the selection process and may contract and expand based on the providers being considered and the stage of the selection process. Many team members will also be a part of the implementation process. The selection team should be large enough so that stakeholders have a voice in choosing the platform, but small enough for you to achieve a consensus on decisions without slowing down.

    Once a selection team is in place, it’s time to set expectations which includes meeting frequency, responsibilities, communication and creating a realistic timeline for selecting the EDC provider. Consider business needs such as upcoming studies, corporate goals and team schedules, training and the implementation process when creating a timeline.

    Stage 2: Define the User Requirements

    A variety of functional areas will rely on different aspects of an EDC platform, which is why you want a selection team to be diverse; to receive perspective into a platform’s requirements. Each selection team member should be tasked with coming up with a list of needs and wants, as well as any items they would not like to have in a system.

    When developing the list of user requirements consider the company’s typical study design:

    • Phase, SAD, MAD, DDI, Cohorts etc.
    • Number of subjects
    • Number of sites and their geographical locations
    • The expected number of case report forms (CRFs)
    • Duration and other specifics such as standard reports
    • The need for safety alerts
    • Vendor data uploads
    • Helpdesk support
    • Data entry screen design flexibility
    • Bulk approval (PI and monitoring sign-off)
    • Query management
    • Medical term coding functionality

    Think about the type of pricing structure that will work best for the company (volume discounts, annual licensing fees, pay by study, etc.). Who will maintain or host the application on a server? Consider other systems used for study management and conduction by your company such as a clinical trial management system (CTMS) and an interactive response system used for randomization. Do you want an EDC system that is compatible with these systems or are you looking to replace the multiple vendors with an all-in-one solution?

    These specifications will drive costs as well as guide your thinking about what features you will need from a provider.

    Stage 3: EDC Provider Meetings and Demos

    Based on the agreed upon requirements, vendors should be invited to meet with the team and demo the applications. If you have requirements that are show-stoppers (such as hosting, pricing, standard reports) it may be a good idea to provide the EDC provider with a quick survey prior to meeting. This way, if the provider cannot meet the non-negotiable requirements you can remove them from consideration and focus on vendors that do.

    When meeting with the EDC providers, don’t be afraid to ask questions based on your experience with other systems, your pain points and based on feedback you have received from site users and partner vendors. At the end of the day, this is an investment and commitment by your company. You want to ensure that you have all the facts to make an informed decision.

    Get a feel for their customer service:

    • Are they responsive and flexible enough to meet your company’s needs?
    • Will you have a dedicated representative you can reach if an issue needs to be escalated?
    • Will they allow you to test drive the system?
    • If you have a feature request, are they at least receptive to the suggestion?

    During the demos, the EDC providers are putting their best foot forward, but you can still gain a lot of insight into their post-sales experience.

    Stage 4: EDC Provider Selection

    You have narrowed down the list and are ready to decide. If you haven’t done so already, now is the time to engage QA to audit the provider and ensure that they can be considered as a qualified provider for your company. You don’t want to sign the EDC provider’s contract only to realize that they do not have validation documentation to support the functionality and regulatory compliance touted during the demo.

    If you are down to two companies and find it hard to decide between the two, take another look at the list of nice to haves/wants. Are there features one provider offers that you may need in the future and the other provider does not? Think about the provider’s company culture. Is one EDC provider more in-line with that of your own company?

    Here at PharPoint we have navigated these waters before and have chosen two different EDC providers, Medrio and Medidata, as our primary vendors. However, our teams are experienced in many different systems and can easily work with any EDC provider a client chooses. We can also help you select an EDC provider that will work best for your company.”

 

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PharPoint Video Series: Ensuring Quality Statistical Output

 

At PharPoint, we pride ourselves on producing quality statistical analyses. How are we so confident in the quality of our product? Find out in this video with Senior Manager of Statistical Programming Tracy Pflaumer and Manager of Statistical Programming Amber Urban.

  • Ensuring Quality Statistical Output Transcript

    “Here at PharPoint research, we pride ourselves on producing quality statistical analyses.

    You may be wondering how are we able to ensure the quality of our product. It all starts with strategic planning of the analysis which includes everything from how the study team for a project is selected to how programming is implemented and reviewed.

    Our extensive use of independent verification and review of all statistical output followed by additional statistical review by our highly reputable statisticians helps ensure that nothing is sent prior to being thoroughly vetted by our experienced team.
    As we mentioned before, it all starts with planning. When a project is awarded, our managers collaborate both within and across functional areas to identify the best leads and team members suited for the project.

    Previous experience with the client, therapeutic area of the project, and even the phase of the project are just some of the considerations taken into account when the study team is chosen. Once the team has been selected, a kickoff meeting is scheduled.

    This kickoff meeting is used to bring team members of contracted services together to discuss the study’s assumption, scope of work, design strategies, timelines, and any other details to ensure top quality deliverables and client satisfaction.

    Once the project gets to the programming phase, our process for statistical programming ensures top quality output. One of our key components to ensuring top quality is our use of custom programming. Unlike others who may use rigid tools or macros to create outputs from a preset library of templates, our use of custom programming allows for ultimate flexibility.

    The other key component to our process is independent programming. Independent programming is our preferred and most widely used method of verifying statistical output. The idea is that one programmer, who is referred to as the production programmer, creates the dataset or output based on the study documents/specifications.

    Separately, another programmer, referred to as the validation programmer, is given the same documents and asked to programmatically recreate the results. That validation programmer then compares the results from the original output using an electronic comparison procedure while also visually inspecting the output. The two programmers work together to resolve any differences between the two results and once all differences are resolved, the results are considered independently verified by double programming.

    As an extra level of validation, if a study is contracted to map the raw data into SDTM (which stands for Study Data Tabulation Model), then any production analysis datasets that are produced are programmed off of the SDTM datasets and the validation side of the analysis dataset is programmed from the RAW data.

    This allows us to provide an extra level of QC to confirm that the data (and therefore the results) are not being altered when it is being mapped into SDTM. This same process would be used any time SDTM is used for an output as well.

    This is a unique part of our process, and we feel is important to ensure the quality of the outputs and results.
    Once the data is final and the statistical outputs are complete (which means they have already been independently verified), the study statistician then reviews for completeness and accuracy. The goal of the review to is to ensure that the outputs are consistent and that they make sense with the data that has been provided.

    This is also used as a means to identify any potential data issues to provide back to data management and to also confirm the outputs are in line with the SAP. Most importantly, we want to ensure the quality of the outputs.”

 

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PharPoint Video Series: How and When to Consider a Data Monitoring Committee

 

Have you heard the following acronyms: DMC, DSMB, DSMC, IDMC and wondered what they stand for? In this video, PharPoint Biostatistician Alison Miller and Senior Director of Consulting Operations Amy Flynt provide you with information that can help you answer this question and many more.

  • How and When to Consider a Data Monitoring Committee Transcript

    “Have you heard the following acronyms: DMC, DSMB, DSMC, IDMC and wondered what they stand for? Or have you ever wondered what is the difference between a DMC and an IDMC? Have you ever wondered if you needed one of these committees for your study and how you should go about forming that committee? Today, we are going to provide you with information that can help you answer these questions.

    These acronyms are all different terms used to describe the same thing; an independent group of experts who monitor patient safety and may also monitor treatment efficacy data while a clinical trial is ongoing.

    This group advises the sponsor regarding the continuing safety of trial subjects and those yet to be recruited into the trial, as well as the continuing validity and scientific merit of the trial. Here is what the acronyms mean:

    • DMC = Data Monitoring Committee
    • DSMB = Data Safety Monitoring Board
    • DSMC = Data and Safety Monitoring Committee
    • IDMC = Independent Data Monitoring Committee

    For consistency purposes we will refer to this group of experts as a DMC for the rest of the discussion today, but any of the previously mentioned acronyms would be acceptable.

    Reasons for a DMC:
    The fundamental reasons to establish a DMC is to enhance the safety of trial participants and if regular interim analyses of the accumulated data are needed. When determining if you need to have a DMC, consider if your study meets any of the following criteria:

    • Large, randomized, multisite studies
    • Controlled trial that compares rates of mortality or major morbidity
    • Known safety concerns regarding adverse events, a specific laboratory parameter for the product, or serious toxicity with the study treatment
    • If there are a priori reasons for a safety concern due to the invasive administering of the study treatment
    • An adaptive design with a formal interim analysis planned
    • If the study endpoint is such that a highly favorable or unfavorable result, or even a finding of futility at an interim analysis might ethically require termination of the study before the planned completion
    • Study being performed in a fragile population such as children, the elderly, pregnant women, or other vulnerable populations such as terminally ill or diminished mental capacity
    • If the trial population is at an elevated risk of more severe outcomes even when the study objective addresses a lesser endpoint
    You would not need a DMC for the following:
    • Trials at early stages of product development
    • If the trial addresses outcomes such as relief of symptoms or something similar that is of less concern than mortality and morbidity

    Selection Process/Forming the Committee:
    The selection of the DMC members is extremely important since the DMC responsibilities relate to the safety of trial participants. The committee should be made up of a minimum of 3 people:

    • A medical doctor who specializes in the area being studied
    • A medical doctor who either specializes in clinical trials or in the area being studied
    • And a statistician with knowledge of statistical methods for clinical trials and sequential analysis of trial data
    PharPoint recommends an odd number of voting members to ensure that the vote does not end in a tie. The committee will also usually have a non-voting statistician who serves as the unblinded DMC support statistician.

    Consider prior DMC experience when selecting your members. Prior DMC experience for the statistician is particularly important if there is only one statistician serving on the DMC. The other main concern to consider when selecting your members is an evaluation of their potential conflicts of interest.
    These could be financial conflicts, study conduct conflicts for investigators enrolling subjects in the trial in which their knowledge of interim results could influence their conduct of the trial, and intellectual conflicts for individuals known to have strong views on the relative merits of the interventions under the study and as such may not be able to review the data in an objective manner.

    Things to consider/Recommendations:
    We recommend that each DMC maintains a charter that becomes the governing document for that committee. This document needs to include well-defined standard operating procedures. Per the FDA Guidance: “Such charters are important for the same reason that study protocols and analytical plans are important—they document that procedures were pre-specified and thereby reduce concerns that operations inappropriately influenced by interim data could bias the trial results and interpretation.” The charter should include the following information at a minimum:

    • Schedule and format for meeting
    • Format for presentation of data
    • Information regarding who will have access to interim data and who may attend all or part of DMC meetings
    • Procedures for assessing conflict of interest of potential DMC members
    • The method and timing of providing interim reports to the DMC
    • Information regarding who is involved in DMC-related activities
    • Define a communication plan to establish who may directly communicate with the DMC (this is often only a DMC coordinator and/or an unblinded DMC support statistician)
    • Roles and responsibilities of the DMC members
    • Roles and responsibilities for other persons involved with DMC related activities (e.g. the sponsor, DMC coordinator, unblinded DMC support statistician)
    • Information regarding meeting minutes
    • Options for DMC recommendations

    Some people may tell you that you must use a different group to run the DMC than the group that does the analysis. This is not the case. What is required is that everything remains independent and the unblinding information is only shared with the approved personnel as stated in the charter. This can be achieved within one single organization if that organization has the necessary firewalls in place.

    In the first 10 years of operations at PharPoint, the biostatistics team has provided independent data review committee support for over 100 different protocols, most which involved multiple meetings. Our statisticians have served the role of both unblinded statistician and voting statistician for these meetings.

    If you are interested in hearing more about DMCs, you need support for a DMC, you need help determining if you need one for your study, or you need help recruiting members, please contact me at 919-433-2474. You can also reach me via email at amy.flynt@pharpoint.com.”

 

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PharPoint Video Series: Smart Database Design

 

Ever wonder what makes a database design “smart”? Or when a sponsor should begin thinking about data collection and analysis? PharPoint Senior Database Programmer Michelle Morcos covers these topics and more in this video.

  • Smart Database Design Transcript

    “What makes a database design “smart”? And when should a sponsor begin thinking about data collection and analysis? We cover that and more in this video.

    Achieving a balance between data capture and data analysis can be tough. The goal of data collection is to provide complete, high quality data. Here we want to consider how database design can ease some of the burden of data entry and monitoring – by being flexible while also reducing entry errors, by allowing for easier entry through intuitive design and by increasing collection efficiency.

    The goal for data analysis is to receive complete, high quality data that is most conducive to the review process. This is best done by maintaining the ability to link data together, by ensuring data quality and consistency, by handling missing or questionable data, and by conforming output to expected standards.

    The challenge we face in database design is meeting the needs of both the database end users and the data consumers. This is where CDASH comes in.

    Designing the database to meet data collection needs up front while reducing the efforts to meet SDTM compliance downstream can be achieved with proper planning and use of CDASH. But there are potential issues even when following the CDASH model so it is critical they be addressed during database design.

    By taking an intelligent approach to CDASH, you can not only make data entry more efficient but also reduce the number of custom edit checks and manual reviews by building the database to allow for enforcement of numeric precision, correct units of measurement, range checks and more.

    Smart database design begins with SDTM compliance and data analysis in mind. This should be considered during form design but it’s never too early to begin thinking about it.

    Ideally this would start at protocol development where the CDISC PRM, or Protocol Representation Model, could be utilized. For instance, why not use CDISC Controlled Terminology right from the start, thereby eliminating the need to map the data on the backend?

    So “Beginning with the End in Mind” is a great way to work when feasible. However, SDTM can still be implemented after all data is collected as part of the submission preparation process. While it’s best to start early, it’s never too late!

    If you’re interested in hearing more about intelligent database design with SDTM compliance in mind or how to bring your existing program of studies into compliance, please reach out to the PharPoint Programming team via pharpoint.com.”