Revisiting the “why” behind decision making can be a helpful exercise in all aspects of business. This is no less true for clinical operations executives when it comes to the clinical trial systems they employ to facilitate their teams’ work.
The technology that supports clinical trial systems has evolved steadily over the past several decades, yet the ultimate goal of streamlining workflows and improving output continues to be a challenge to different degrees across small, midsize and large pharma companies.
As newer, more user-friendly systems debut, clinical operations executives may benefit from reassessing whether their current systems are adequately meeting their trials’ needs. With improved technologies, smaller companies could increase their teams’ capabilities. Similarly, large companies may benefit from adopting newer systems in an attempt to stay innovative and competitive.
Below are some categories of clinical trial systems that sponsor companies should regularly assess as they determine whether their clinical trial needs are being adequately met.
Electronic Data Capture (EDC) System or Clinical Database
The EDC system is considered to be the main home of the “official” clinical trial data set. Study subject data that are required for the study analysis are entered by the clinical site and maintained in the EDC software. Output from the EDC can be viewed as tables, listings and figures (TLFs), and when combined with data from other systems (e.g. the central lab database), they are useful for analyzing study findings. For registrational trials, much of the EDC data eventually gets submitted to relevant health authorities for review and approval.
Things to consider:
- Who will manage the EDC system?
- Ideally, a person or group experienced in data management, system configuration, software updates and managing user access should be assigned to manage the EDC system.
- This can be a sponsor data management group, outsourced data management group/CRO, sponsor clinical operations group, or any combination of the above.
- Ideally, a person or group experienced in data management, system configuration, software updates and managing user access should be assigned to manage the EDC system.
- Complex vs simple
- Ensure that the selected EDC can meet the specific demands of the trial.
- Consider if you need extra functions like triggered pages, various logs, or a protocol deviations module.
- Ensure that the selected EDC can meet the specific demands of the trial.
- Ease of navigation
- Not only does the EDC need to be easy to navigate by the sponsor or CRO team, but most importantly, it needs to be easy to use by the clinical site, where the bulk of the data entry is being done.
- If clinical sites perceive that navigating the system is complicated, they will be less likely to update it in a timely manner.
Interactive Web/Voice Response System (IWRS/IVRS/IXRS)
IXRS are also configured and programmed to fit each study protocol and are used for a range of investigational product (drug)-related activities including trial subject registration, randomization or stratification of trial subjects to different trial arms, tracking of depot and clinical site drug inventories and expiration dates, and subject drug dispensation.
Things to consider:
- Not all studies use an IXRS
- If an IXRS is not used in a study, its usual activities must be performed manually using a spreadsheet or in conjunction with certain fields in the EDC. This can become time consuming and tedious for the clinical operations team.
- User Authorized Testing
- Since drug dispensation is so critical from a safety and data quality perspective, sponsors must perform user authorized testing (UAT) to catch algorithm or design errors before the system goes live.
- This is a time-consuming activity, so consider how much UAT help the IXRS suppliers are willing to provide. Some vendors will create custom scripts that testers can follow without much hassle while others aren’t willing to provide anything at all. In the latter case, either your company’s clinical operations or clinical drug supply group must create their own scripts.
Electronic Trial Master File (e-TMF)
Good clinical practice (GCP) requires that study sponsors maintain an organized record of their clinical trial conduct. This system of records is known as the study’s Trial Master File, or TMF.
Health authorities, such as the FDA or EMEA, reserve the right to inspect clinical trial sponsors or sites at any time, and will most likely do so following a registrational filing. While an inspector can choose to focus on any aspect of the trial, most will at least spend some time reviewing the TMF. Therefore, it’s important to have a complete and reconciled TMF at any given time (i.e. missing vs expected documents).
As recently as a decade ago, most sponsors were maintaining paper TMFs, but now, e-TMFs have become standard. Filing and retrieval are arguably more convenient in an e-TMF and inarguably, better for the planet.
Things to consider:
- e-TMF review
- One of the most tedious and time-consuming part of maintaining an e-TMF is the regular (typically quarterly) review that clin ops teams must do to ensure that a) all expected documents are filed and b) that of those documents, that they’re classified correctly and are accurate.
- When considering a system, ensure that documents are easy to file and classify, and that it has features that easily facilitate regular reviews.
- Extra document features
- Some e-TMF systems have extra features such as document authoring, e-signature, etc. Consider if you really need these or if your office suite is sufficient.
Clinical Trial Finance Software
Clinical trial finance software may help sponsors with any of the following: subject reimbursement, subject stipends for travel and other trial-related costs, site budget creation, site budget invoice payments, and any related oversight costs.
While sponsors using CROs can outsource these activities to the CRO, having an in-house finance system gives sponsors more control over payments and provides better financial oversight overall.
Things to consider:
- Who will set up, manage, and benefit from the system?
- Will it be clinical operations, your company’s finance group, or a combination of the two?
- Either way, your finance group may need to at least be involved in system setup as some of these systems facilitate payment from the sponsor’s bank account.
- Are all end users allowed to use the system?
- Depending on the functions deployed, the users of the system could be site subjects, clinical sites, your finance group, or your clinical operations group.
- Ensure that the system meets the needs of all end users.
- For example, if you plan to allow your ex-US sites to use the system to request site payments, ensure that their finance groups allow this instead of following their traditional invoicing method.
Clinical Trial Outsourcing Software
This newer category of software has the potential to save sponsors time and money by systematizing and standardizing the vendor (supplier) selection process to allow sponsors to better understand the value of each vendor. Frequently, especially at smaller companies, there is no process, forcing the decision makers to rely on gut feel only or unequal spreadsheet cost comparisons.
Clinical trial outsourcing software may help with several steps of the procurement process: proposal creation, vendor evaluation, bid/proposal comparison, selection, contracting, and management. These systems may also help with study budgeting and forecasting.
Things to consider:
- Vendor evaluation parameters
- What quantitative and qualitative factors does the system take, or allow the user to take into account when evaluating vendors, e.g. cost, reputation, size, unique offerings, etc.?
- Proposal standardization
- How does the system allow an equal comparison across vendors in the same category when each proposal may break down costs and value differently?
- Collaboration features
- As vendor selection may be a collaborative effort between a company’s procurement/outsourcing group, and the end user group (for companies that have the latter), how will the system facilitate this collaboration?
Risk Management Software
With the rise of risk-based and centralized monitoring, risk management software was developed in parallel to support these approaches.
Risk management software can flag statistical outliers in clinical data (e.g. those stored in databases such as the EDC). Some systems also allow tracking, classification, and risk scoring e.g. using the RACT model.
Things to consider:
- How will risks be communicated and resolved?
- Do you have an in-house central monitoring group, or will another group use the system? Who will this group raise issues to (QA, CRAs, etc.), and who will mitigate those issues?
- Duplication
- If you have a CTMS, it may already have a simple risk management module.
Patient Recruitment Software
Traditionally, sponsors have used clinical sites to do the bulk of the subject recruitment for the clinical trial. Subject recruitment is the biggest pain point when it comes to clinical trials and can make or break a trial. And for certain therapeutic areas, clinical site recruitment just isn’t enough to meet enrollment goals.
To meet this need, in the past several years, many patient recruitment vendors and software have cropped up to help supplement site recruiting by bringing patients from other sources, whether it be social media or real-world data.
Things to consider:
- Software vs service
- Some patient recruitment systems come bundled with services while others primarily offer a system for the sponsor’s use.
- Are you looking for a self-service system that just identifies where the subjects are? Or do you want the vendor to provide full service (subject identification, referral to clinical site and/or consenting, etc.) with the related technology just to track subjects?
- Specialization
- Consider the purpose of the system – to diversify recruitment, recruit for a specific therapeutic area (e.g. rare disease, oncology, healthy volunteers), or recruit in certain countries.
- Ensure that the system you choose meets, or even better – specializes in – your purpose and criteria.
Office Software
People don’t typically think of standard office tools as being “clinical trial software”. However, it’s hard to imagine how teams would collaborate without email, instant messaging, word processors, slide decks, or cloud storage.
Examples of Office Software:
- Office suites: Microsoft 365, Google for Business
- Project Management software: Asana, Monday, Basecamp
- E-signature software: DocuSign, HelloSign, Adobe e-sign
Things to consider:
- Office software is generic by design
- It is meant to be used by all types of businesses across all industries. This makes it flexible, but it also forces you to customize tools for your needs.
- For example, if you want to track many of your clinical trial activities in a spreadsheet, the onus is on you to structure these spreadsheets and maintain them.
- You can always hire an expert to customize some of these tools for your company, but this will require many conversations with busy clin ops end users. Ultimately, these tools may still appear somewhat stitched together, not purpose-built, and somewhat manual.
Clinical Trial Management System (CTMS)
CTMS are designed to step in where office suites leave off. This broad category of software attempts to help clinical operations or cross-functional trial teams oversee trials, primarily focusing on maintaining site contact info and high-level site and subject information. Some CTMS even attempt to help with clinical finance operations.
The earliest CTMS were based on Customer Relationships Management (CRM) systems that are used by sales teams. The problem is, conducting clinical trials is functionally dissimilar to conducting a sales process. In clinical trials, numerous intricate data-related workflows must in managed whereas in sales, the emphasis is on managing numerous relationships at different stages.
CTMS is typically deployed by companies that are in the process of scaling their trial pipeline, and who cannot manually maintain all their processes using office software alone. Unfortunately, CTMS are not typically automated or easy to use or of accommodating all key trial information. This can negate much of the purpose for which they were deployed.
Sponsors employing CROs can “use” the CRO’s CTMS for the life of a trial. However, they typically can’t directly access the CTMS to configure it, use any features, or do powerful data aggregation. They, at most, get spreadsheet outputs that are pre-defined by the CRO.
Things to consider:
- Double the work
- Does your team have sufficient bandwidth to make the best use of a CTMS?
- Most CTMS have to be supplemented by manual spreadsheets. Will your team have time to maintain both?
- Return on investment
- How much will you have to manage the technology rather the technology helping your team?
- Will the technology help senior management, CRAs, or clinical trial managers?
- Will the technology actually make things more efficient? Or will it add to the “system overload” that clin ops teams already face?
Decentralized Trial Solutions
The Covid-19 pandemic accelerated many industry trends that were already in motion. One of these is the emergence of decentralized trials.
Decentralized trials move clinical trial activities away from the clinical site and keep them local, to the subjects’ home. Clinical trial “visits” or data collections are then conducted via telemedicine, mobile nurse blood draws, or wearables such as smart watches. Decentralizing trials can make trial participation easier and more appealing for subjects.
Decentralized trial solutions can help facilitate any of these processes, whether it be pulling wearable data into a dashboard, allowing subjects to electronically consent to a study, or allowing clinicians to perform physical examinations via teleconference.
Things to consider:
- To what extent can your trials be decentralized?
- More complex therapeutic areas studying dynamic disease processes such as oncology are harder to decentralize. The same goes for phase 1 (first in man) studies where adverse events are unknown.
- These subjects must be monitored more frequently in a more intensive way. Also, certain procedures, such as CT imaging, need to occur in a clinic.
- In these cases, a decentralized solution isn’t necessarily needed.
- Decentralized trial technology vs services
- When going the decentralized route, depending on the trial protocol, technology may need to be supplemented by services such as mobile nursing and phlebotomy.
- New DCT-centered processes and SOPs may also be needed to integrate the technology, services, and internal workflows into a cohesive whole.
Clinical Trial Analytics Software
These software are designed to help clinical trial managers and executives discover, interpret and communicate significant data patterns derived from the studies they oversee.
These patterns are primarily displayed in the form of highly visual dashboards and reports. These can be used to display various study statuses (sites activated, subjects enrolled, depot IP inventory, risks) and enable teams to see how a study is doing at a high level.
Things to consider:
- Setup Efforts
- How much scoping and customization would be required for the system to deliver on the specific trail needs? Does someone on your team have the time and expertise to do this?
- As with office software, generic products require lots of customization and in the end, can appear stitched together.
- While some widgets can be created visually, using drag and drop, the most powerful and useful widgets and dashboards require programming.
- Even analytics software dedicated to clinical trials can require lots of work to scope and set up, particularly if the vendor project managers don’t have clin ops experience.
- Design Sensibility
- Good analytics dashboards require the designer to understand a) what are the most important analytics to track on a trial and b) what are the minimum analytics needed to tell a full story. Having too many dashboards and widgets ends up creating noise and clutter that detracts from the user’s rapid understanding of actionable insights.
- Who will make these design decisions?
- Data Refresh
- Analytics dashboards require frequent refreshing to stay relevant. Otherwise, your team is left with static and therefore, stale insights.
- Consider how the data will be refreshed, who will refresh it, and the effort taken to refresh it.
- Duplication
- CTMS dashboards may already be providing analytic functions, so consider if/how the analytics software will supplement those.
- Analytics software can typically supplement CTMS and spreadsheets but is too high level to replace them as means of study oversight.
Clinical Operations Oversight Software
Combining the best of office tools, CTMS, clinical trial analytics software, and workflow automation, a clinical operations oversight solution is meant to decrease the number of systems that a clinical operations team needs to navigate their work.
ClinOps Pro is the only one of its kind and uses innovative design to support the clinical operations function by providing clin ops teams and executives with higher quality insights and workflow automations.
ClinOps Pro provides complete oversight and does not need to be supplemented with numerous spreadsheets or other tools. ClinOps Pro was designed by clinical operations professionals who understand critical, yet complex clinical operations workflows.
How should clinical trial sponsors design their technology ecosystem?
We at Seascape are, of course, huge proponents of deploying technology for the greater good.
While many of the technologies listed above have improved trial efficiency, some have also introduced specific problems. Historically, earlier technologies have been known to cause clinical operations teams to become overwhelmed, leading to high turnover and burnout. And we all know that repeatedly doing the same things will bring the same results.
By adopting more modern technologies, clinical operations teams can establish an innovative culture and reap huge gains.
Things to consider:
- Consider new, innovative technologies rather than reflexively adopting status quo options
- How do system interoperability and integrations affect daily workflows?
- What are some potential benefits of having a particular function or oversight managed by the sponsor as opposed to a CRO?
- Is the system purpose-built or does it seem too generic?
- “Fire bullets, then cannonballs” – it’s worth trying one system on one small study before deploying it enterprise-wide to be sure that it works for the company.
Each team and company is different. But if sponsors start thinking about technology in a similar way that they do site activation or patient recruitment, this may result in breakthroughs in those critical activities as well.
