 covers many themes throughout the calendar year, it seems as if the common denominator is typically data. As I wrote in this space last month, our editor Andy Studna attended the 13th annual DPHARM: Disruptive Innovations to Modernize Clinical Research conference in Boston in September. Unsurprisingly, the main theme was innovations—specifically clinical trial solutions. Of course, there were many such innovations on display that focused on data collection. How does all of this data-talk fit into our November issue, which focuses on contract research organization (CRO) and sponsor relationships? In the new world order of multiple vendors in the clinical trials space, there are more solutions available, more methods of collecting data; more of everything it seems. How are CROs and sponsors handling all of this and how are they keeping the quality of data in check? That's the prevailing question we explore in this issue.

Speaking of collecting data, Studna recently returned from Barcelona, Spain, where he covered the SCOPE Europe conference. Coverage, including video footage of a panel he moderated on electronic clinical outcome assessment, can be found on our 

 focuses on new CRO/sponsor partnership and outsourcing models that have gained popularity in recent years. These arrangements have added even more complexity to what I mentioned above. To tackle these dynamics, CROs and sponsors are creating strategic relationships that emphasize a shared partnership culture and operational strategy. The article explores approaches in managing these partnerships. Our next 

 also examines this relationship evolution, but provides a unique cautionary look at the 11 key "warning signs" to watch for that could impact CRO/sponsor success. Rounding out our trio of November features on this theme is an 

 on streamlining clinical trials. With all of the new challenges CROs and sponsors are facing, service providers can step in to help with the goal of creating efficient and more patient-focused trials.

Articles

Publisher's Note

How important are relationships when it comes to efficiently managing clinical trials?

Relationships in the Current Landscape 

In the past decade, the clinical research industry has experienced a proliferation of new outsourcing models and operational strategies in which contract research organizations (CROs) and sponsors are working in more integrated ways. Against the background of the increasingly complex clinical research landscape, we have seen a rise in strategic partnerships and partnership-driven approaches to outsourcing as a way to navigate that complexity and more effectively deliver clinical trials.

Now more than ever, developing a shared partnership culture is important to support the more complex strategic objectives and operative functions that keep clinical trials humming.

In this constantly evolving clinical research landscape with global trials that are only growing in size and intricacy, managing relationships with vendors and maintaining internal staff is an important element of successful operations. To support these efforts, sponsors and CROs alike can leverage certain tools and strategies for assessing and characterizing vendor relationships to identify opportunities within the outsourcing strategy.

One such tool is the typical nine-box model for performance assessment, which we have adapted to fit the characteristics of sponsor/vendor relationships (see Figure 1 below). In the adapted version, the complexity of the strategic demands and the cultural positioning of the relationship map across the x and y axes. Assessing partnerships with this model allows you to map them into low, mid, and high sectors, generating a more precise determination of their current state and requirements.

With this understanding, it becomes easier to guide decisions on investment, alignment, and strategy. It can also reveal opportunities to scale strategic complexity and capitalize on industry changes and advancing technology, or it can steer investments in cultural alignment to bolster operations within the partnership.

Not every vendor relationship must track to the high sector of the nine-box model and operate as an integrated partnership. For example, a “tactical” dynamic with low strategic complexity is focused on simple execution and, therefore, won’t require the cultural integration of a high-complexity agile partnership.

However, clinical research is a large-scale, complicated field with global stakeholders. With the consolidation in the CRO industry, many partnerships now include global CROs and large pharmaceutical sponsors with needs that span broader scopes. The regular incidence of changing roles and role definitions, globalizing tasks, changing outsourcing strategy, implementing multiple types of strategy within a single partnership, or leveraging multiple partners all add layers of intricacy that then require more cultural alignment to achieve success. In effect, this requires a strategic shift toward the high sector of the nine-box model. Mapping your partnership to the high sector means you have cultivated cultural alignment across organizations and agility within the outsourcing strategy. In practice, this agility may include multiple outsourcing strategies within a single partnership to best fit each situation’s specific needs.

Partnerships within the high sector require a dynamic relationship with continuous assessment and adjustment to maintain the cultural alignment that underpins the operational agility.

The main pillars and key metrics of partnership culture for high-complexity and functioning teams are alignment, branding, and control—or what we refer to as the ABCs of partnership culture. Aligning both companies around shared vision, mission, and values with high-level leadership commitment, backed by clear objectives and targets, sets the tone for achieving those shared clinical research goals. Deliberate, considered branding efforts solidifies and reinforces a combined identity for the partnership while unified control measures ensure accountability.

In what can feel like a stark contrast against the clear, objective, and scientific setting of clinical research and the traditionally contract-execution approach to outsourcing, successful players in the industry are tapping into the “human” side to drive efficiency, consistency, and alignment. Not every aspect of cultural alignment can be translated and measured with typical controls. As such, there is an element of tuning in and knowing what it should feel like.

In harmonized outsourcing partnerships, it can feel like trust in deep personal relationships at all levels. In complex high-sector outsourcing models, the goal is to align across roles and experience levels between the partner organizations, but differences will exist. With an aligned culture of partnership, both parties can trust everyone to work together to identify and resolve issues within a shared framework.

Of course, there will always be challenges. But when organizations are aligned, they can create solutions together. When there is a cultural incongruence between organizations, the dynamic can tend toward feeling more combative than collaborative, or a certain resistance emerges that limits forward momentum. This pulls focus and energy and redirects it to assigning blame before seeking solutions, or the issues are hidden rather than communicated directly. When each organization has invested in establishing their own core cultural values, however, it provides a solid base for the partnership.

Trust and a true sense of alignment are essential to high-performing partnerships, but it is important to back those with metrics to maintain operational excellence within a well-controlled partnership. Carefully selected key performance indicators (KPIs) can better illustrate the correlation between strategy and operational achievements. However, ill-fitting KPIs can skew decision-making or lead to a misallocation of vital resources. Identifying the right KPIs can drive mutually valuable outcomes, provide a rallying point for cross-organizational efforts,and encourage teamwork while generating precise, transparent data that can trigger corrective action to help course-correct. For agile partnerships running large, challenging, or intricate studies, KPIs serve the partnership best when shared, as opposed to two sets of metrics divided and tracked between organizations.

Choosing partnership metrics that provide the right sets of data for governance can be challenging. ICON has identified four foundational categories that bear meaningful metrics: finance, quality, operations, and relationship health.

Each of these categories can be further divided into specific operational metrics that reflect more granular levels to fit the outsourcing partnership’s goals and needs. The four categories of metrics that support mutual success in strategic partnerships:

Turnaround times for work order development

Monitoring turnaround time for closing out action items

Quarterly two-way surveys (or one-on-one interviews) to measure the satisfaction of both teams, including opinions on training, onboarding, and operating processes

Transparency across these metrics is crucial for a trusting, cohesive partnership whether the results are trending positively or negatively. With the same data in hand, teams can problem-solve together around the shared objectives and within the same framework to ultimately arrive at solutions that minimize risk and drive success. This is especially important when multiple outsourcing models are deployed within a single relationship.

Understanding the unique requirements and expectations of each outsourcing strategy across vendors or within single partnerships is vital to their success. The complexity of the clinical research landscape is a fact that continues to evolve, driving the variety of outsourcing models and operational strategies that increasingly depend on partnerships to run efficiently.

Applying these tools and methods to understand and optimize these relationships between sponsors and vendors will continue to be a critical component of delivering clinical trials effectively.

ice president, strategic alliance management, ICON plc

Feature Articles

A shared partnership culture is critical in navigating today’s complex terrain.

Harmonizing Outsourcing to Keep Clinical Trials on Track

The landscape for clinical trials is ever evolving.

 Adaptive trial designs, decentralized, and hybrid trials are becoming more prevalent, particularly in light of the COVID-19 pandemic.

 Regulatory changes in the US and abroad are constant and inevitable.

As clinical trials change, the relationships between contract research organizations (CROs) and sponsors have evolved as well. Both entities have needed to respond to the trends noted above, and deal with issues such as staffing challenges, remote work, and multiple vendors (e.g., electronic data capture, central labs, core imaging labs, etc.).

Throughout it all, the relationships between sponsors and CROs remain critical to clinical trial success.

 Although there are many environmental, technological, and regulatory changes occurring in the clinical trial space, the basics of CRO and sponsor relationships still apply.

From the perspective of the CRO, the optimal sponsor client is friendly, engaged, responsive, respectful, and communicative. In fact, it is in the CRO’s best interest to ensure that the sponsor relationship is healthy and productive.

Conversely, sponsors choose their CRO partners very carefully. Oftentimes, they send out requests for proposal (RFPs) to several vendors and have a process for narrowing down to their chosen CRO. As with CROs, sponsors want to work with those partners who are capable, communicative, and responsive.

Unsurprisingly, CROs regularly perform systematic internal reviews of their clients’ projects. Often included in these reviews are assessments of the relationships with the sponsor client. One component of project reviews done at former CROs engaged internal discussions around a list of “warning signs.” These signs were meant to give a heads-up to management of factors that either make the project difficult to execute or point to the possibility of the CRO losing the project or client.

These warning signs can be instructive for how sponsors and CROs interact.

Part of the appeal of medical device clinical research is working with cutting-edge products. Because these devices are so innovative, there may be no similar devices on the market and, therefore, the CRO understandably has not worked with thetherapy or product class. This can require creative thinking with study design and conduct (within regulatory requirements) and perhaps with the FDA itself, but such resourcefulness can appear to the sponsor that the CRO staff are inexperienced.

While the sponsor should be the expert on their therapeutic area and product, very often (especially with startups) they are not experts in clinical research. Part of the CRO’s job is to educate clients in compliant study conduct.

It’s been the author’s (hard-earned) experience that clients who show a win-lose mentality while negotiating the consulting agreement extend that same attitude to relationships during the project. It becomes difficult when the sponsor continues to be overly demanding during the clinical study. The CRO should be looking out for the best scientific and regulatory interests of the sponsor, but this can be misinterpreted as obstructionist.

Conversely, difficult contract negotiations with the CRO can foreshadow a team that is rigid in their thinking and performing in a “cookie cutter” manner.

CROs, like any business, need a steady revenue stream to survive. Startup organizations are often key customers for CRO services, since many lack the necessary talent and experience in the clinical research area. Startups are sometimes tenuously funded, and it is important for the CRO to keep an eye on accounts payable as well as work with the company to find the most efficient and less costly way for execution to keep the costs within the company’s budget.

Of course, sponsors need to perform due diligence not only on the financial health and track record of a prospective CRO partner, but on appropriate staffing levels and historical performance.

4. Client timelines expectations vs realistic timelines

More often than not, sponsors push the deadlines for their clinical trials onto the CRO based on business needs and promises to investors rather than a realistic timeline for the respective trial. The study timelines depend on several factors that might not be in the CRO’s control, such as site contract negotiations and enrolling the right participants. It is important during the bid, as well as throughout the study duration, to keep track of project timelines and communicate any changes to the sponsor while mitigating any potential delays and risks.

Conversely, CROs may need to calibrate their expectations. While the CRO may have the ability and motivation to move quickly, the sponsor may have constraints (e.g., budget, manufacturing, etc.) that prevent moving full speed into their clinical study.

5. Client questioning invoices/overly cost conscious

To be clear, clients should scrutinize their CRO invoices carefully, as clinical studies are a huge investment. It becomes excessive, however, when every line item and expense is questioned, and the CRO needs to put aside work to answer excessive questions. In an optimal relationship, the level of invoice detail should be reached early in the process and hopefully questions can be minimal.

As an analogous situation, a CRO’s over-reliance on frequent change orders can test the sponsor relationship. It is natural for project scopes to creep, and documented changes should be able to be billed to the sponsor. How refreshing it would be, however, if all CROs responded to RFPs with realistic study budgets instead of the lowest number in order to win the business. CROs also need to communicate typical reasons for change orders with their clients and think about how often they send them; perhaps changes in scope can be saved for quarterly updates.

Personnel change is an unfortunate reality of life. It’s fair to expect a strong working relationship can be established over time between the CRO and sponsor teams. When this balance is upset, it can be for the better, but very often, it is for the worse. New sponsor managers frequently want to establish themselves in their company and often the CRO is an easy target.

Not only do sponsors despise (and rightly so) changes to management in the CRO, but changes to the project team members are equally disliked, due to the retraining and onboarding of new study staff. It is incumbent upon CRO management to create working environments that help with employee retention, but also to keep a project team together for as long as possible. When change is necessary, a clear plan and communication with the sponsor is critical.

In any client/consulting relationship it is always easier to work with one point of contact. In reality, many sponsors have a group with which the CRO team works. It becomes problematic (going both ways) when a member of the sponsor team overrules a previous decision, or multiple decisions are handed down. The best way to mitigate this situation is to establish communication pathways and document it early in the process, hopefully at the project kick-off meeting.

Due to the nature of the sponsor-CRO relationship, the CRO most likely will guide the sponsor (if necessary) on decisions related to the study. From the sponsor side, it is critical, however, that there is one ultimate point of contact at the CRO, and a route for escalation of any issues that may arise.

8. Client/CRO slow to respond/unresponsive, or missing deadlines

As in any relationship, if one side is too busy or slow to respond to requests, questions, or action items, it can make progress on the project impossible. A meeting of all stakeholders can be helpful. Sometimes, however, for good reasons, the sponsor is genuinely too busy to give attention to the CRO. Understanding the sponsor’s situation can go a long way, and perhaps the CRO can be granted greater decision-making authority. However, the sponsor is ultimately responsible for the study and, thus, it is desired that both sides agree to the course of action, or even more critical in case of risk mitigations.

Slow and/or unresponsive can indicate a CRO that is having trouble attracting or retaining staff or has taken on more work than they can handle. The author has experience working in organizations with high rates of attrition, making those who stay responsible for shouldering an ever-increasing burden while trying (at times, desperately) to hire more staff. It can be a vicious cycle of CRO staff burnout and poor performance for their clients.

Micromanaging is the opposite of the previous issue. This is a detrimental situation that can undermine the success of the project because it indicates a lack of trust in the CRO. If the sponsor doesn’t trust the CRO, they may be planning to find another. Also, if not mitigated promptly, this can have downstream effects on CRO staff who may feel disempowered to do their jobs. As with other situations, a frank meeting with stakeholders and management can sometimes help this situation by finding out the root cause of the sponsor distrust and CRO addressing the sponsor’s concerns.

CROs are not generally able to micromanage their clients, but this could manifest itself in an overly detailed project timeline. If a CRO has this tendency, they could be documenting every perceived misstep, and become excessively defensive about who was responsible for any missed milestones (and ultimately costing more money as the CRO bills for this time).

10. Client/CRO not disclosing or discussing information

As with the situation noted above, hiding key information (such as product performance issues) from the CRO staff indicates a lack of trust.

Also noted, the optimal sponsor-CRO partnership is one of regular communication and updates. Some sponsors, want to “throw the study over the wall” to the CRO and not engage with them during the study at all. On the other hand, some CROs assume that any questions or communication from the sponsor constitutes “meddling” in their business. The best way to avoid problems of this nature is for sponsors to engage with the CRO and require regular team meetings and/or status reports.

When a CRO project manager recommends sound courses of action (perhaps on a good clinical practice or site management issue) and sponsor repeatedly does the exact opposite, it signals a lack of trust, which makes progress on a project difficult.

It is the CRO’s job to do what the client wants, as long as it complies with the principles and requirements of good clinical practice. Difficulties can arise when there is disagreement between the parties of what constitutes compliance. CROs, while mandated to conduct ethical and valid research, need to listen to the unique needs of each of their sponsors.

Having reviewed the warning signs from both perspectives, here are five suggestions to establish trust and enhance the sponsor-CRO relationship.

Many issues around invoices, payments, and change orders can be mitigated upfront with a proposal or statement of work that accurately reflects the assumptions, tasks, and budget needed to accomplish the study.

Expectations around roles and responsibilities. 

These should be confirmed and documented at the kickoff meeting to avoid any gaps or duplication of effort. These can be revisited periodically throughout the study.

 It’s important to establish communication channels early in the project. Not only how to communicate, but how often (hourly, daily, or weekly). Communication promotes trust.

 Should be established early and documented. Anything that could affect the timeline should be communicated transparently by each stakeholder.

. A sample invoice should be provided to the sponsor around the time of study kickoff. Hopefully any changes can be resolved prior to the first invoice.

In summary, the principles noted above point to the need, as with any relationship, for the early establishment of clear communication and trust. The ability to work together in good faith and clearly communicate when issues arise is critical.

Director, Clinical Operations, MEDIcept, Inc.

Bhatt A. Evolution of Clinical Research: A History Before and Beyond James Lind. 

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3149409/

Clinical Research Trends & Insights for 2023. WCG. 

https://www.wcgclinical.com/clinical-research-trends-insights-for-2023/

Henderson, L. The State of CRO and Sponsor Relationships 

https://www.appliedclinicaltrialsonline.com/view/state-cro-and-sponsor-relationships

Halloran, L.Measuring the Health of CRO-Sponsor Relationships. 

https://www.lifescienceleader.com/doc/measuring-the-health-of-cro-sponsor-relationships-0001

Exploring the 11 key ‘warning signs’ that could impact partnership success.

The Evolution of CRO and Sponsor Relationships

The process of developing life-altering treatments for patients in need is a complex endeavor. Clinical trials, the essential gateway to medical innovations and drug approvals, are often plagued by challenges that prevent successful completion. It is common for patient enrollment issues to halt a trial before it even starts. According to a report by Biopharma Dive, 85% of all clinical trials fail to recruit enough patients, while 80% are delayed due to other recruitment problems, such as patients who are too sick to participate.

Even when a trial achieves successful recruitment and enrollment numbers, a challenging path toward study completion still lies ahead. Participation issues are not exclusive to the enrollment phase alone; they permeate every stage of the trial process. Approximately 30% of patients drop out before the study is complete.

 This low retention rate places a financial burden on pharmaceutical sponsors and contract research organizations (CROs), slowing the speed of bringing new treatments to market.

This article delves deeper into the challenges faced and explores how service providers are positioned to revolutionize the landscape, leading toward increasingly efficient and more patient-focused trials.

Understanding the drivers of recruitment and retention issues

Clinical trials serve as a vital lifeline for patients across the globe, offering hope to those suffering from debilitating illnesses lacking effective treatment options. However, recruitment and retention remain complex issues for trial sponsors and CROs. Currently, more than 300,000 clinical trials worldwide are searching for 40 million participants, one factor contributing to the rising costs of clinical research.

In theory, trial participation may seem appealing, but in reality, patients experience various logistical, financial, and emotional burdens that can negatively impact participant recruitment and retention rates.

Despite the US providing over two-thirds of global trial participants, recent statistics reveal that only 32% of registered trials are exclusively conducted within the nation’s borders.

 This type of trial design results in many studies requiring some kind of travel, creating an additional layer of complexity. Participants must consider logistics such as securing flights, booking hotel accommodations and ground transportation, and even more demanding logistics such as passport and visa services or long-term stays abroad with entire families. This travel burden is often in addition to navigating differences in language and culture. These complex planning and logistical arrangements add a layer of difficulty to the patient’s medical needs, often making participation seem impossible.

Cross-border and local travel requirements can often lead to severe financial burdens for clinical trial participants, as the out-of-pocket costs associated with study participation can add up quickly for the patients and their caregivers. Incidental charges such as transportation to and from the study site (including air, rail, and ground transportation), meal expenses, and additional internet or cellular data charges while overseas can often seem overwhelming to an individual struggling with a severe disease. Even if these expenses are reimbursed, patients may not be in the position to make the initial payments necessary to begin the trial process.

It is also essential to account for the income lost due to time off work. Trials can extend over several months or years, and many individuals are unable or unwilling to forgo their earnings for such a duration. When faced with extreme financial challenges, many patients opt out of participation in clinical studies.

The idea of undergoing unproven treatments, facing potential adverse effects, and uncertain outcomes can trigger fear and concern in prospective trial participants. An independent study from Clincierge found most patients said participating in a trial was stressful for themselves or their families.

 Over 80% of patients reported that despite feeling excitement related to participation, they also had feelings of anxiety, uncertainty, and frustration. These complex emotions are often rooted in the overarching challenge of managing the trial process alongside their ongoing medical needs.

As clinical site staff and researchers concentrate on the medical and scientific aspects of the trial, the responsibility of managing the tasks mentioned is frequently placed on patients and their caregivers. Thus, the hesitancy of a patient to commit to clinical trial participation is not unreasonable.

The economic and human impact of trial disruptions

The central goal of clinical trials is to develop effective treatments that enhance the quality of life for patients suffering from chronic illness. In many instances, researchers’ primary aim is to eradicate a disease. Nonetheless, the return on investment remains a pivotal factor for trial sponsors and CROs. Losing a single patient during a trial means giving up crucial data and extending timelines, often resulting in significant financial repercussions to the sponsor and CRO. These costs are exacerbated in studies involving rare diseases, where the pool of qualified participants is significantly smaller.

Recruitment and retention problems are cumulative and often result in trial delays. Delays negatively impact study costs and future sales.

While financial losses are often top of mind for trial sponsors and CROs, it is also imperative to recognize the human impact of inefficient trials. A substantial portion of a drug’s ultimate success can be attributed to the contributions of trial participants, as without their involvement, novel treatments would not achieve widespread commercialization. This idea compels us to consider a fundamental question:

If clinical trials hinge on the ability to engage and retain patients throughout a study, how can we proactively mitigate participation risks and strengthen trial performance? It is worth exploring how service providers can play a role in addressing this challenge.

Sponsors and CROs rely on various external service providers to support their research and allow for better trial management. While data services and technology solutions are often the first thing these companies prioritize, these initiatives do not directly address the challenge of patient engagement and high drop-out rates; however, a transformative shift is occurring. Dedicated patient support services in the form of a patient concierge are a positive, disruptive change in the industry.

Much like a hotel concierge, a patient concierge manages all logistics involved in trial participation. Having a concierge level of support makes a trial much less intimidating for patients, their caregivers, and their families. These services include:

Itinerary planning (flight and rail tickets, hotel accommodations, ground transportation)

Reimbursements for meals, incidentals, mileage, tolls, and parking

Long-term housing and relocation services

Apart from overseeing the intricacies of trial coordination, the patient concierge provides consistent support for patients and caregivers from study enrollment through completion. When surveyed by Clincierge,

 95% of patients and 98% of caregivers said having a single point-of-contact to assist them in the trial was crucial. Ideally, these coordinators are local to the patient, live in their time zone, speak their native language, and understand their local nuances, as local coordinators are better equipped to address unforeseen circumstances impacting the patient’s region.

With the assistance of service providers such as patient concierge companies, the path to expedited, patient-centric, and efficient clinical trials become increasingly promising.

Decentralized Clinical Trials: Are We Ready to Make the Leap? Biopharma Dive. January 29, 2019. 

https://www.biopharmadive.com/spons/decentralized-clinical-trials-are-we-ready-to-make-the-leap/546591/

Considerations For Improving Patient Recruitment Into Clinical Trials. Clinical Leader whitepaper. 

https://www.clinicalleader.com/doc/considerations-for-improving-patient-0001

Patient Centricity on Trial. Havas Lynx Faze whitepaper. 

https://havaslynx.com/thought-leadership/patient-centricity-on-trial/

Global Participation in Clinical Trials Report. FDA. July 2017. 

https://www.fda.gov/files/drugs/published/2015---2016-Global-Clinical-Trials-Report.pdf

Amplifying Patient Voices in Rare Disease Trials. Clincierge. 

https://info.clincierge.com/hubfs/Amplifying_the_Voice_of_the_Patient_Ebook_6.8.22.pdf?_ga=2.21457662.450838734.1697564438-1902252478.1664547082

How service providers are helping to accelerate drug development.

Streamlining Clinical Trials: Mitigation and Management

Clinical research, like raising children, often requires a village. It involves numerous stakeholders, from sponsors and sites to participants and vendors, all with their roles and responsibilities. With more players come complexities, but the fundamental principles of transparent communication and goal alignment remain vital for successful trial management. Trust-based relationships form the cornerstone, underpinned by early expectation setting, goal congruence, frequent communication, and a shared commitment to mitigating risks.

Credibility is a must in all business relationships. In sponsor-CRO collaborations, credibility-building starts in the proposal and bid defense stages. Commitments made during these early discussions set the stage for trial setup and execution. Sponsors choose CROs and vendors based on their perceived ability to deliver on these commitments. While there’s a temptation to present a rosy picture to secure the work, overpromising is risky and can erode credibility. Clinical research is inherently unpredictable, and aligning expectations and goals among stakeholders, with frequent progress assessments, facilitates early risk identification and collaborative recalibration.

Many sponsor-CRO relationships start with foundational assumptions about the scope of work, timelines, and costs. These assumptions should be rigorously tested, informed by data and experience, and refined to establish the collaboration’s baseline goals. Goals and milestones often have interdependencies. For instance, CROs depend on sponsors to provide the final protocol before site initiation, while sites need ethics committee approval and executed contracts to activate the study. Seemingly minor delays in any of these activities can lead to significant delays. Alignment on critical milestones and frequent progress reviews, therefore, enable early issue identification and timely resolution.

Clinical trials seldom go exactly as planned. Delays in study start-up, such as site activation delays, can impact patient enrollment. Therefore, daily comparisons of actual data to assumptions help identify gaps, triggering a more in-depth examination of variances, providing process improvement opportunities and allowing for course correction.

Data and technology are also equally crucial for setting goals, planning, and tracking metrics. Accessible data for all stakeholders ensures transparency and allows for early intervention.

While we recognize the importance of transparent communication, shared commitment, goal alignment, and joint risk mitigation, there are often friction points that can disrupt active collaboration. Usual conflicts that occur are around timelines, enrollment assumptions, and project finances—and misaligned expectations are at the root of these issues. Project timelines are affected by various factors, including site identification, regulatory reviews, site contracts, site activations, enrollment, and data collection. Despite best efforts, some phases take longer than expected, leading to challenges. Project finances can be a point of dispute. Some changes in scope can be acceptable, However, budget increases due to incorrect assumptions, such as enrollment delays or site additions, are harder to justify when the scope hasn’t changed. Frequent communication, transparency around assumptions, and continual metric evaluations prevent surprises and eases these discussions.

Not all stakeholders share the same motivations, experiences, resources, or financial backing. Understanding these differences is crucial for setting the right expectations. Small biotech companies with limited resources may make requests that significantly affect the study’s conduct and budget, while larger sponsors may be more accommodating. Key opinion leaders in large academic institutions might be desirable, but their lengthy start-up timelines could be a hurdle. A CRO may not fully grasp the budget constraints of a small-sized sponsor—and recognizing these distinctions is vital.

In the complex landscape of clinical trials, strong relationships among diverse stakeholders are mission-critical. Aligning on goals, setting expectations, proactively addressing challenges, and consistently evaluating progress fosters transparent communication and highly collaborative relationships that can navigate the challenges that arise on the road to success.

A Closing Thought

Trust-based relationships form the foundation for successful trial management. 

The Two Guiding Principles of Optimal Trial Delivery

The value proposition for the electronic implementation of patient-reported outcome (PRO) measures (PROMs) is well established, but the migration and implementation of measures initially developed for paper administration requires careful consideration and demands adherence to what has been either defined or recommended as best practice.

In recent years, the Electronic Clinical Outcome Assessment (eCOA) Consortium members have observed a high number of sponsors implementing electronic PROs (ePROs) in their clinical trials having to locate, digest, and compare a range of different documents and resources pertaining to ePRO implementation best practices. In its previous incarnation as the Electronic Patient-Reported Outcome (ePRO) Consortium, several papers were developed that made substantial contributions to the literature,

 and in combination with key papers developed by ISPOR,

 they together described the core of best practices in the field.

However, even that consensus-developed work could not be classified as definitive and complete, as other important scientific works developed by organizations such as Oxford University Innovation

 and papers generated by select groups of experts contributed to what could collectively be labeled as “best practice.” What has long been required is a consolidation of these best practices that represents the true consensus.

As is the way with technological progress today, the capabilities of electronic devices utilized for ePRO data capture has advanced substantially, yet documented best practices have not kept pace with these advancements. Therefore, any definitive work must ensure contemporaneousness as far as possible.

To address the critical need for an authoritative, consensus-developed and technologically-relevant resource for ePRO best practices, the eCOA Consortium developed the 

Best Practices for the Electronic Implementation and Migration of Patient-Reported Outcome Measures

This consolidation of best practices articulates the vital need to align with measurement comparability requirements and regulatory guidance, as well as recognition of where usability for the individuals completing these measures can be optimized.

Balancing maintenance of the scientific integrity of a measure with optimized accessibility is critical.Transparency is key in this step-by-step guide detailing the key system and screen design requirements for successfully implementing ePROs as well as best practices. Detail is provided about whether a given practice is rooted in evidence or expert consensus, thus enabling those utilizing the practices to take a fully informed, considered, and standardized approach to implementation. Screenshots depicting the practices are provided throughout, to ensure shared understanding, and a flow diagram guiding those implementing ePRO through the process and the key design decisions.

Ultimately, this work serves as the true consensus on the best practices for ePRO migration and implementation, endorsed by the 23 eCOA technology or allied service providers that form the eCOA Consortium.

However, publication does not signal the end of this effort—socialization of the best practices among all stakeholders is crucial to truly facilitate standardization of ePRO implementation. PRO measure copyright holders and instrument authors are key to ensuring the widespread adoption of these best practices, and to mitigate the risk of any specific implementation guidance being at odds with those outlined by the Consortium, it is important to effectively communicate the updated best practices and their rationale to these key stakeholders. Furthermore, clinical trial sponsors are responsible for ensuring that the data they capture are fit for regulatory submission.

ePRO data are an increasing component of regulatory submissions, so the adoption of the most up-to-date best practices to ensure optimal data integrity is critical.

We believe this single point of reference will serve as a blueprint for the industry for many years to come, and we look forward to this resource being adopted by all those engaged in the field of eCOA. Though we must not become complacent, there is still research to do, and best practices should evolve as the evidence base expands.

Authored on behalf of Critical Path Institute’s eCOA Consortium by Florence Mowlem, PhD, Vice President, Science, ObvioHealth, and Scottie Kern, Executive Director, eCOA Consortium

O’Donohoe P, Reasner D, Kovacs S, et al. Updated Recommendations on Evidence Needed to Support Measurement Comparability Among Modes of Data Collection for Patient-Reported Outcome Measures: A Good Practices Report of an ISPOR Task Force. 

. 2023 May;26(5):623-633. doi: 10.1016/j.jval.2023.01.001.

ePRO Consortium. Best Practices for Migrating Existing Patient-Reported Outcome Measures to a New Data Collection Mode. Published 2018. 

https://c-path.org/wp-content/uploads/2022/02/BestPractices3_Migrating.pdf

ePRO Consortium. Best Practices for Electronic Implementation of Response Scales for Patient-Reported Outcome Measures. Published 2018. 

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https://doi.org/10.1016/j.jval.2023.10.007

Data Collection

eCOA Consortium develops new resource for best practices.

A New and Comprehensive Guide to ePRO Migration and Implementation

Harpreet Gill, head of decentralized clinical trials (DCTs) at Icon, is working to make DCTs more easily implemented and more commonly used throughout the industry. She recently spoke with 

Pharmaceutical Executive: Can you explain the importance of decentralized trials?

 As the time has gone on over the last few years (and we know the pandemic accelerated this) there's been a greater need to think about the different ways to engage patients in clinical trials. There's an element of efficiency there in terms of how data is collected. One of the things that we are seeing is that there are more clinical trials, but there aren't as many patients there are interested in being involved because it can be difficult to be involved. We do need more patients, but we also need greater diversity as well. All of those factors are now really driving the importance of decentralized clinical trials in the in the clinical trial setting, but also if you take a look at healthcare generally we are relying more and more on digital tools. Folks are more interested in taking care of their own health and managing their own and I think we need to take a look at how we can use and manifest and surface that in a clinical trial setting as well.

PE: What struggles have you faced trying to implement DCTs?

 There are a number of hurdles that we face when trying to implement decentralized clinical trials. Firstly, it's a making sure there's good understanding of what we mean by decentralized clinical trial. There are a lot of definitions out there. Some people think it's telehealth, some people would say it's consent, and others think it's about carrying out one or more of the assessments that would normally happen at an investigator site away from the site. So, making sure that people understand what we're trying to do in that in that context can be a little bit of a challenge. There is definitely some education that needs to be done for sites, patients, and sponsors while also helping the regulators understand what we're doing and how we're trying to implement DCT. That's a work in progress.

Also from a technology perspective, some of the technologies that we wanted to use are novel, so ensuring that so that they'll work very well and that they're operationalized end to end, you need expertise and there's not been a huge amount of expertise in the past. That is changing, but it's a work in progress. It's not something that you can answer immediately when you're using a completely different technology. It's important to think about investing in pilots and engaging earlier with doctors, people, and sponsors that are willing to give things a go early on before you've got everything proofed out.

Then there's the sites and their view on decentralized clinical trials. Our experience is that they are interested but concerned about how this will work just in terms of the day-to-day management of the clinical trial. What does that mean in terms of their responsibilities and accountabilities? It's a business for many sites, so how does this affect their business model? There are some of the things that we're trying to address.

PE: How important is it to have good communication among these sites and how do you build that communication?

There are a number of ways. We need to ensure that the sponsors are fully engaged, and at the outset work with the sites, remind them that this is going to be a DCT or a hybrid study and that they'll be novel technologies used. This also involves gauging their expectation, enrolling them into the process, and get an understanding of their concerns. It also includes making sure that when we look at the site contract, we ensure that they are going to be properly reimbursed for what they need to do as far as the trial is concerned. We're able to offer direct support for the sites as they go through the clinical trial, both in terms of providing training for them and a concierge support team who can engage with the site and ensure that the site understand that if they've got questions around the technology and how things are progressing, they've got someone to reach out to, almost an extension of the of the study coordinator. There are some of the ways that we can engage.

Gill discusses her continuing work to transform clinical trials and improve the patient experience through DCTs.