Andrew Schafer

Every service provider wants their customers to be satisfied with a completed engagement. In that case, knowing what drives customer satisfaction with an outsourced project would be helpful to know, right? Industry Standard Research’s 

Late Phase Study Trends and Market Outlook (2016-2020)

 report digs into key factors behind customer satisfaction as well as many other dynamics within the Late Phase market.	 	Late Phase decision-makers rank 

 timelines management as the attribute that contributes most to a sponsor’s satisfaction with a CRO’s Late Phase services. The provider must deliver according to timelines to have a happy sponsor at the end of a project. Following this is 

, another metric tied to timeline efficiency during a project. If sites and patients cannot be recruited in an effective and efficient manner, both timelines and study budgets will suffer, resulting in a less than pleased customer.	 	Drivers for CRO selection and drivers for satisfaction do not necessarily go hand in hand. The reasons why a CRO is chosen for work may be very different from what will make a sponsor feel satisfied with a finished project. While 

 is the most important driver of sponsor satisfaction, a similar attribute, 

Confidence the provider will meet timelines

, is only middle-of-the-road when it comes to importance in the provider selection process. A similar example may be selecting a handyman to complete odd jobs around your house. You might hire a handyman based on their experience and knowledge but if that handyman takes a month to fix a leaky faucet, you are not going to be a satisfied customer.	 	

“In your experience with CROs and Late Phase services, what usually drives your satisfaction with CRO performance? Rank the following from most important (number 1) to least important (number 8) to your satisfaction with CRO performance.”

	 	ISR has also gathered insights regarding a host of other topics in the Late Phase space including:	

		Late Phase company spend for the past 12 months and projected spend in 2020 by study design (Interventional trials and Observational research) and by study type (Post-marketing Safety studies, Health Economics and Outcomes Research, and Expanded Access studies)

		Outsourced proportions of Late Phase work for the past 12 months and projected proportions in 2020 by study design and study type

		Key decision-makers for various components of the Late Phase study outsourcing process

		Selection drivers for providers across multiple types of Late Phase studies

		Late Phase trends including the importance of technology, the pervasiveness of EMR data, the global nature of studies, and the use of existing vs. newly collected, purpose-driven data

 report is designed to assist those interested in the Late Phase market in not only remaining current with market happenings but in getting a jump on what the market is expected to look like in 2020. Learn more about the report at: 

https://www.isrreports.com/reports/late-phase-study-trends-market-outlook-2016-2020/

Articles

This recent report explores key factors behind customer satisfaction and other dynamics within the Late Phase market.

Late Phase Study Trends

We can’t read the future, but we can certainly help you make smart decisions heading into it. Industry Standard Research (ISR) has come out with a new report that shines a light on both the current state of the Phase II/III clinical trial market as well as its anticipated direction into 2020. “Phase II/III Study Trends and Market Outlook (2016-2020)” contains analysis of emerging trends, Phase II/III spend, and outsourcing behaviors that are expected to shape this realm in the coming years. Both sponsors and service providers will gain information they can utilize to situate themselves effectively for the expected twists and turns in a future market.  	 	One important take-away from this report concerns the increasing relevance of the developing world in the Phase II/III sphere. Decision-makers foresee a notable shift of Phase II/III studies from developed markets into emerging market regions in the coming years.	 	

Increases are also anticipated for emerging market patient recruitment, of which further analysis can be found in the report. These findings indicate that the future of the Phase II/III market will likely be marked by a change in regional demographics and terrains. The expected trend will call for a strong understanding of clinical spaces across global territories, and an increased cultural competence moving forward in Phase II/III endeavors. Altogether, the findings in this report paint a robust picture of foreseen market behavior for industry decision-makers. 	 	

“Phase II/III Study Trends and Market Outlook (2016-2020)”

 provides in-depth accounts from 112 high-level pharmaceutical and biotech decision-makers responsible for Phase II/III drug development activities within their companies.  For sponsors, use this report to know what your industry peers expect for their business direction and study investments, and understand how your company’s strategy compares to that of your competition. 

, the report will inform you of the capabilities and services expected to be sought in a future Phase II/III market. Move forward knowing where to bolster your capacity. 	 	So stay ahead of the game and make informed decisions for your business’s future. More information on ISR’s “Phase II/III Study Trends and Market Outlook (2016-2020)” can be found at: 

https://www.isrreports.com/reports/phase-iiiii-study-trends-and-market-outlook/

Report shines light on the current state of the Phase II/III clinical trial market and its anticipated direction into 2020.

Phase II-III Market Dynamics

	We all need help sometimes. For pharmaceutical companies, this often comes in the form of a reliable and competent contract research organization.  The sweeping presence of CROs across the pharmaceutical landscape opens numerous opportunities for sponsors and providers looking to begin or continue collaboration in clinical development. With ever-increasing procedural complexity of clinical development activities, provider outsourcing becomes a powerful tool. However, one size does not fit all when it comes to the best outsourcing philosophy for a sponsor’s clinical development needs and specifications. Priorities ranging from budget to emerging market reach greatly impact the optimal outsourcing model for the job. ISR’s

 Clinical Development Outsourcing Models (2

helps pharmaceutical sponsors gain a comprehensive understanding of how to identify the outsourcing model most compatible with the priorities of their company. CROs will understand current user perspectives on a number of outsourcing models and arm themselves with the knowledge and insight to succeed going forward in their clinical work. 

Clinical Development Outsourcing Models (2

 provides detailed insight into sponsors’ selection drivers, usage, and overall experience/satisfaction amongst seven outsourcing models. 107 respondents were surveyed for this report, all of whom must 1) work at a pharmaceutical or biotechnology company with an annual R&D expenditure of at least 100 million dollars, 2) have responsibility for outsourcing clinical trials, and 3) be sufficiently knowledgeable about their company’s clinical development outsourcing model.

	While respondents report a generally high level of outsourcing within their company, the level of reported satisfaction with their current provider model adds an important layer to consider. Indeed, findings indicate that a substantial proportion of respondents are not fully satisfied with their CRO model. Only 35% of those surveyed 

that their company has found the ideal outsourcing model.

	In Search of the Ideal Outsourcing Model

	The consistently high use of outsourcing in clinical development work speaks to a deep and ongoing relationship between pharmaceutical sponsors and CROs. However, the reservations voiced by the majority of respondents indicate, at a high level, that many sponsor organizations are still in search of a suitable outsourcing method for their clinical development needs. For sponsors, you have a number of outsourcing approaches to consider when deciding on the type of model that will best fit your clinical development needs. Use this report to understand the nuances of each to better suit your requirements. For service providers, the report findings will provide insight concerning the aspects of clinical development work that pharmaceutical companies hold highly when choosing an outsourcing model. Applying this information will enable you to work seamlessly with your sponsor by anticipating their needs accordingly.

	The nature of outsourced clinical development activity today is a multi-fold process that begins with a clear understanding of the CRO’s capabilities and the sponsor’s clinical development needs. The ability to recognize the optimal outsourcing model for a sponsor’s development work is key in creating productive, efficient relationships between parties. ISR’s 

 report provides a comprehensive means for sponsors and providers to enter into clinical development activity with a sense of confidence in their outsourced approach.

 report, please visit ISR’s report page at: 

http://www.isrreports.com/reports/clinical-development-outsourcing-models-2nd-edition/

Andrew Schafer is the President of Industry Standard Research.

We all need help sometimes. For pharmaceutical companies, this often comes in the form of a reliable and competent contract research organization.

Only 35% of Sponsors Have Met Their Outsourcing Match

	Accuracy in data capture methods has always been and will continue to be a foremost necessity in pharmaceutical clinical trials. It is therefore no surprise that the markets for Electronic Data Capture (EDC), Electronic Clinical Outcome Assessments (eCOA), and Electronic Patient Reported Outcomes (ePRO) are growing given their capability to collect large amounts of data while simultaneously ensuring high quality. ISR’s

 EDC and eCOA/ePRO Market Dynamics and Service Provider Performance (2015) 

report shines a light on this increasing technological trend by providing a greater understanding of EDC and eCOA/ePRO penetration in pharmaceutical markets. Sponsors, CROs, and technology providers will gain perspective on how to situate themselves in this market.

EDC and eCOA/ePRO Market Dynamic and Service Provider Performance

 offers a view of provider performance on a number of core attributes and gives a close-up perspective of sponsor, CRO, and clinical site service experience with EDC and eCOA/ePRO organizations. Data were collected from 166 respondents representing 3 groups: study sponsor companies, CROs, and clinical research sites.  An important take-away from this research concerns the increasing acceptance and use of EDC and eCOA/ePRO technologies amongst sponsor companies and CROs. Findings show that 91% of respondents exhibit a greater preference towards EDC than paper CRFs, a preference increase of almost 15 percentage points from two years earlier. Similarly, 86% of respondents report a preference of eCOA/ePRO over paper diaries compared to a 61% preference in 2013. The majority of respondent’s reports that they will further increase their use of these technologies in the coming years.  

	Such a vast difference in the preference between electronic and paper-based methods not only indicates a realization of the potential benefits gained through the use of electronic technologies, but also points to a fairly clear gravitation away from paper-based methods. This trend of increased acceptance and usage has several implications for both sponsor/CRO companies and technology providers. 

, be aware of growing demands for technological services within the clinical trial arena. Prepare for additional adoption of your services and possible expansion of your sponsor’s preferred provider list. 

be sure that you have an understanding of the breadth of providers available in your use of data collection technologies. Our report is available in order to provide a clear sense of the best provider for your needs and area of focus. 

	Understanding the emerging area of electronic data collection technologies is a necessary step towards navigating the changing landscape of pharmaceutical clinical trials. The efficiency and quality provided by EDC and eCOA/ePRO allows providers and sponsors alike to move forward with a sense of assurance in their work

 EDC and eCOA/ePRO Market Dynamics and Service Provider Performance (2015)

Accuracy in data capture methods has always been and will continue to be a foremost necessity in pharmaceutical clinical trials.

eCOA and ePRO Provide Accuracy in Data Capture

	It is well known within the industry that being on a sponsor’s preferred provider list affords a critical leg up to providers hoping to win business. Phase II/III work is no exception. In the 7

 edition of Industry Standard Research’s 

CRO Quality Benchmarking - Phase II/III Service Providers

 report, ISR digs a bit deeper into the dynamics of preferred provider lists and how these lists affect CRO selection for Phase II/III studies.

“Does your company have formal preferred provider agreements for Phase II/III services?” 

	Two-thirds of respondents relay that their company utilizes formal preferred provider agreements for their Phase II/III work.  However, when these data are examined by company size, it becomes obvious that large sponsor companies rely on these lists much more so than their smaller counterparts.  83% of large sponsor organizations utilize PPAs compared to 53% of mid-size sponsors and only 14% of small sponsors.  CROs would do well to recognize that fighting for a spot on the preferred provider list at large organizations is a critical undertaking but might not even be an available option at the mid-size and smaller companies. 

	ISR also collected insights into how preferred provider lists impact the criteria used to select a CRO for Phase II/III work to test the hypothesis that providers are gauged differently based on whether the sponsor company (a) is selecting a CRO from a preferred provider list, (b) has a list of preferred providers but is selecting a provider not on that list, or (c) does not have a preferred provider list. Though some attributes such as 

 are considered important regardless of the decision-making scenario, the data have uncovered meaningful differences regarding selection drivers in each of the aforementioned scenarios.

	For example, among respondents who are selecting among their preferred providers, 

 does not crack the top four most important attributes when selecting a Phase II/III provider while it ranks as more important when sponsors are selecting a non-preferred provider or when they do not use PPAs. ISR postulates this is due to the sponsor organization already having become comfortable with the CROs’ therapeutic expertise during the process of adding each provider to the preferred provider list.  This means when a CRO is bidding for work in a situation where it is already on the preferred provider list, the CRO may not need to spend significant time convincing the decision-making team of its expertise in the desired therapy area but can instead focus on featuring other critical capabilities.

	ISR provides further analysis regarding selection criteria and preferred provider dynamics as well as detailed service provider performance metrics in its 

 It is well known within the industry that being on a sponsor’s preferred provider list affords a critical leg up to providers hoping to win business. Phase II/III work is no exception. In the 7th edition of Industry Standard Research’s CRO Quality Benchmarking - Phase II/III Service Providers report, ISR digs a bit deeper into the dynamics of preferred provider lists and how these lists affect CRO selection for Phase II/III studies.

CRO Quality Benchmarking

	Despite the substantial difficulties associated with orphan drug trial recruitment, this segment of the drug development market is booming.  By 2020, orphan drug sales are expected to make up 19% of prescription drug sales, excluding generics.  In ISR’s 

Orphan Drug Market Dynamics and Patient Recruitment Best Practices 

report, ISR provides an overview of the orphan drug development market as well as how to best drive patient recruitment in an area of drug development in which drug developers do not want to be left behind. 

report, ISR interviewed 10 orphan drug development experts and collected quantitative data from 96 survey respondents from pharma companies that develop orphan drug compounds.  One of the takeaways featured in the report and consistently mentioned by interviewees is the varying preference for orphan drug experience.  The degree of this preference is driven by the type of work that is being outsourced.  The more logistically driven the outsourcing components, the more advantageous it is to seek third-party providers with orphan drug experience.  However, if the components being outsourced are more medically driven, targeting providers with therapeutic expertise is advantageous--particularly since regulations are therapeutically focused.

“If your company were to outsource an orphan drug/ rare disease trial, would it prefer a CRO that….”

	In all cases, orphan drug experience was preferred by a lower percentage of respondents than the alternative (therapeutic experience and global experience).  The takeaway for sponsors is that they should consider exactly what aspects of the clinical trial are being outsourced.  If the sponsor plans to outsource the advertising, marketing, and recruitment of an orphan drug trial, ISR found that it may be worth exploring the option of working with a company that specializes in orphan drug trial recruitment--a company that knows the best practices for reaching these patients--as opposed to the medical expertise required to treat them.  What this means for CROs and recruitment specialty providers is 

 that orphan drug experience does not matter, but that therapeutic expertise, and global operations capabilities should not be abandoned from your positioning in exchange for orphan drug experience.  Framing orphan expertise almost as if it is an additional therapeutic area is one way ISR found companies have included orphan drug experience as a service offering.

	The recruitment of patients for orphan drug trials adds levels of complexity to the already difficult process of patient recruitment.  Navigating the space as a sponsor, CRO, or specialty provider requires careful consideration of what activities need to be outsourced, which recruitment outlets need to be utilized, and how to navigate an often complicated regulatory environment.  ISR’s 

report explores these topics and further provides industry recommendations and best practices for those involved in the intrinsically onerous task of orphan drug trial patient recruitment.

Despite the substantial difficulties associated with orphan drug trial recruitment, this segment of the drug development market is booming.

Improving Orphan Drug Patient Recruitment

Interactive Response Technology (IRT) incorporates both interactive voice response systems (IVRS) and interactive web response systems (IWRS). IRT systems are used at sites to optimize drug availability by managing data of patient diaries, drug and patient randomization, drug supply, and much more. Overall, these systems are designed to provide sponsors the opportunity to run more efficient trials in terms of both time and cost. However, as trials become more global and more complex, IRT systems are expected to handle more data coming from a variety of sources. Are these systems meeting user expectations? The short answer is “sometimes.” Along with cost challenges, ISR found that sponsors want more user-friendly systems, need faster start-up times, and require integration with other eClinical technologies. Spoiler alert: most IRT systems are not meeting user expectations in terms of eClinical integration.

2014 IRT Market Dynamics and Service Provider Benchmarking report

”  in which 24 IRT vendors (including in-house systems) were rated by 105 users across 20 system attributes. Anticipating that integration would be a challenge with eClinical technologies, ISR decided to take the unique approach of benchmarking IRT vendors’ integration with 20 EDC vendors, 14 ePRO vendors, and 29 CTMS vendors. This provides a closer look into the eClinical space, focusing not only on use and selection but on integration as well.

Many of the questions answered in this report offer projections regarding the utilization of IRT services as well as what sponsors would like to see improved as the IRT market moves forward. The number one improvement listed in this report is “Integration with other systems” and roughly half (48%) of respondents aren’t integrating their IRT systems at all. This “integration gap” affords IRT service providers a real opportunity to differentiate their offerings. 

The chart below shows the trends in IRT integration. ISR asked respondents with which eClinical technologies their company has integrated IRT application(s). Respondents were able to select multiple integration points. (Base = 105 respondents)

Spoiler alert: most IRT systems are not meeting user expectations in terms of eClinical integration.

IRT Market Dynamics and Service Provider Benchmarking: Market at a Crossroads

“The only constant is change.” This famous quote has been attributed to people ranging from Heraclitus, an ancient Greek philosopher who lived ~100 years before Plato, to Francois de la Rochefoucauld, a French author. Those of us who have spent considerable time working in the CRO industry have our own version of a “constant” and that is constantly asking the same question: What is the size of the CRO market? 

The difficulty in accurately answering this question comes from the current and historic dynamics of the industry. The CRO industry is still relatively young, highly fragmented, and a considerable proportion of the industry consists of private companies. ISR has wanted to release this report for several years and what tipped us over the edge was the decision by Quintiles to re-enter the public market. Estimating an industry market size without a clear understanding of the financial position of the market share leader seemed irresponsible. 

Over the past several years, the pharmaceutical industry has witnessed a relative flattening of R&D spending. No longer can CROs and service providers count on increasing R&D budgets to fuel their growth. Growth now has to come from (1) a continued increase in outsourcing penetration and (2) stealing market share from competitors. That said, CRO revenues and backlog continue to rise as a result of the rising proportion of development dollars being outsourced.

“2014 CRO Market Size: 2012-2018” report

 in which the CRO market is projected to reach $23.6B in 2014. This report looks the CRO market from the top-down and segments the spending by phase (I-IV), geography, and service line. With a 7.9% CAGR from 2014 to 2018, CROs are benefiting from the increased rate of outsourcing and increasing R&D budgets from biotech and specialty/ generics companies. 

Those of us who have spent considerable time working in the CRO industry have our own version of a "constant" and that is constantly asking the same question: What is the size of the CRO market?

CRO Market Size: Growth in a Flat R&D World

Risk-Based Monitoring – Beyond Theory In-Depth Review

The April edition of Applied Clinical Trials contained the article “

What Does the Future Hold for Clinical Monitoring?”

 in which Industry Standard Research’s (ISR) President, Andrew Schafer, examined a range of industry perspectives across a number of alternative designs and monitoring processes. With ISR’s newest market research report (“

Risk-based Monitoring: Industry Guidance on Adoption, Use, and Outsourcing

”) Mr. Schafer is back to draw comparisons and share data from their latest survey. 

Well, if you ask marketing and branding experts, they will tell you a name can be everything. At ISR, we have found it interesting that someone in the pharmaceutical industry named a process for monitoring investigative sites and patient data “risk-based monitoring.” For an industry that is notoriously risk-averse and highly regulated, we would have bet against a solution named “risk-based monitoring” gaining traction. But it has.

How does the industry’s awareness and interest in RBM compare to other monitoring models?

 While not as widely known as triggered or traditional on-site monitoring, 95% of respondents report that RBM is gaining momentum in their organization. But why are RBM trials gaining momentum? In two words: Lower Cost. The vast majority of respondents who have experience with RBM studies indicated the catalyst for running these trials was to lower the monitoring costs. And CROs take note: 72% of respondents who have direct RBM experience indicated their organization does save money using risk-based monitoring.

The awareness of and interest in RBM is relatively high. Sponsors are, or should be, doing their due diligence on the topic. They are looking for both internal subject-matter experts across many different disciplines within their organization and for CROs who not only have experience operationally executing RBM studies, but they are looking for CROs who can/ will input on the design and strategies surrounding them.

: ISR’s “Risk-based Monitoring: Industry Guidance on Adoption, Use, and Outsourcing” surveyed 78 individuals from sponsor organizations with responsibility for the design, conduct, and outsourcing of RBM trials. This report offers insights into sponsors’ interests and use of RBM models, factors that are driving adoption, and study types seen as best fits for these types of studies.

More information about ISR’s report is available at 

http://www.isrreports.com/product/risk-based-monitoring-industry-guidance-on-adoption-use-and-outsourcing/

With ISR?s newest market research report (?Risk-based Monitoring: Industry Guidance on Adoption, Use, and Outsourcing?) Mr. Schafer is back to draw comparisons and share data from their latest survey.

ISR Reviews Report "Risk-based Monitoring: Industry Guidance on Adoption, Use, and Outsourcing"

When you are through changing, you are through."  So says Bruce Barton.  Bruce who? Think Betty Crocker. She's Barton's creation. So are the enduring household reputations of Campbell Soup, Revlon, General Motors, and General Electric. Barton is among the most successful advertising executives in American history—some insist, the best. A real forward thinker for most of the 20th century. 

If Barton were alive today, he would be all over the results of a recent Industry Standard Research (ISR) Study* evaluating what clinical monitoring might look like in 2015.  

Why? We know that the biopharma industry is not what it was five years ago as financial pressures continue to mount. Second, we know that clinical monitoring can account for approximately half the costs of later stage clinical development projects, so if companies are going to cut costs, they might as well target the biggest bucket.  

That being said, survey results reinforced that traditional clinical monitoring will not go away. It can't. Its scope is a critical component to help ensure squeaky clean data and utmost patient safety. Yet, according to study results, if sponsors and service providers are to relieve stubborn industry-wide financial pressures and meet growing industry demands, clinical monitoring must begin to morph into more of a hybrid model—at least in the later phases of clinical trials. As one respondent aptly put it, "There is a large area of opportunity to improve how clinical trials are conducted. Hopefully the combination of new technologies and alternative models can help to improve monitoring and data quality." 

Consider these study results a wake-up call to action. The report details the overall awareness, interest, and likelihood that alternative models would be adopted for clinical monitoring; it exposes the barriers to adopting these models; it outlines appropriate phases of development for the various mix of monitoring models; analyzes the best pricing models for this highly outsourced activity; and broadens the industry's understanding of how the clinical monitoring environment will likely change over the next few years.  

While the biopharmaceutical industry can be slow to change, current commercial forces are working to accelerate the adoption of adaptive monitoring designs. These forces (a struggling economy, lack of novel drugs in the pipeline, mega mergers, sub-par financial performance, and the patent cliff) will impact clinical monitoring, just as it has impacted other facets of biopharma.  

Many companies saw the handwriting on the wall early on. In the late 1990s, Novella Clinical began to test new monitoring models, utilizing EDC for both data capture and remote review. Today, Novella utilizes a combination of on-site and centralized monitoring to effectively monitor clinical studies.  On-site monitoring allows monitors to assess study documentation, compliance with protocol, staff training, and source documentation, while a centralized monitoring team, through its data coordination center (DCC), provides remote data review and coordination.  

"By leveraging the two groups we have developed a targeted monitoring approach that increases centralized monitoring with a corresponding decrease in on-site monitoring," explains Novella's Nick Dyer, Executive Vice President of Business Development.   

"The targeted monitoring plan is designed by planning to monitor a random sampling of selected patients and/or specific data points.  Centralized monitoring through our DCC provides remote data review and coordination in support of the field monitoring staff.  By having the DCC review these patients, much of the normal data inconsistencies will be cleaned prior to a monitor ever visiting the site; and through our centralized review, any study data trends are addressed.  In addition, the constant review of data coming in through the EDC system improves follow up with sites, which translates into improved data entry metrics and faster query generation and resolution." 

As a consequence, the trend Novella is seeing is an increased sponsor comfort with their hybrid centralized/on-site monitoring models, as more organizations are willing to utilize a targeted on-site monitoring model in combination with the centralized data review team. 

Generally, sponsors maintain some monitoring function with internal staff. Yet, according to survey results, the majority of biopharmaceutical companies (92%) rely on outsourcing to support their monitoring functions. 

That degree of outsourcing will not change. Sponsors indicated they plan to continue to utilize monitoring support from the same mix of service providers they use today, i.e., CROs, temp and contractor staffing agencies, and BPOs.  

In terms of the mix between in-house and outsourced clinical monitors, the mix will shift slightly more in favor of outsourced monitors. The current mix showed roughly 40% to 60% (in-house versus outsourced), and the mix by 2015 will likely be in the 30% to 70% range.  

While this is good news for service providers, the question is, how will they differentiate their clinical monitoring services? Based on CRO media, it seems they are already attempting to differentiate themselves by developing newer, non-traditional models in order to offer a more customized approach to clinical monitoring. 

Aptiv Solutions, for example, has developed specific technology (AptivAdvantage™) and work processes geared toward adaptive clinical trials. Phil Birch, Corporate Brand Manager for Aptiv, explains the company's differentiation is its technology and execution processes. "Particular emphasis has to be placed on complex adaptive design trials, which provide the highest value information to aid development decision making. Complex design trials will revolutionize drug development." 

Premier Research, on the other hand, focuses its efforts on electronic data capture. "We feel that EDC will provide the best scalable solution that is both flexible and automated for a centralized point of tracking, while providing near real-time remote/centralized access to site data and metrics and retain the high quality that is required," notes Patrick Young, Executive Director, Clinical Trial Management and Clinical Monitoring Services.  

"We are continuing to review and assess more efficient and effective centralized approaches to clinical monitoring that will improve both time and cost without reducing data quality. Our primary focus will always be the quality of data and ensuring that it does not suffer in the pursuit of efficiency." 

Figure 1. Study results indicate that although respondents are substantially less aware of the triggered, on-site model, they are just as interested in it as they are in traditional, regularly scheduled on-site monitoring. 

While these newer approaches to clinical monitoring are being utilized by some, how aware of, and interested in, them are sponsors and service providers? As you can see from Figure 1, study results indicate that although respondents are substantially less aware of the triggered, on-site model, they are just as interested in it as they are in traditional, regularly scheduled on-site monitoring. 

Moreover, Figure 2 suggests that while most respondents currently use a traditional approach, which is likely to continue through 2015, more significant growth is projected to come from the triggered and remote, centralized approaches—45% and 107% growth respectively. 

Figure 2. Utilization of three monitoring models today and in 2015. 

 Scott Houston, Director, Clinical Operations at Omeros, a Seattle-based biopharmaceutical company, describes his company's use of alternative monitoring models as one that starts with a comprehensive monitoring plan and includes data management and medical review, as well as centralized remote clinical review and cleaning of EDC data. "We anticipate and achieve less CRA hours spent per patient with this additional level of centralized site support and management, without a reduction in total monitoring oversight.  Intensive management of site data entry and query resolution provides relief to CRA workload while on-site, and a quick and early avenue for addressing data trends across sites and the study.  This is very important in a fast-moving trial. Centralized targeted review of screening data prior to randomization, including inclusion/exclusion criteria, concomitant medication, and medical history, provides the sites an additional and welcome level of support in screening for eligible subjects. The sites have responded to us with very positive feedback." 

Figure 3. Quantitative web-based survey of highly screened individuals who have responsibility for clinical  monitoring activities within their organization. 

Clearly, while there is very solid interest in non-traditional models, study results indicated that not all models are best suited for all development phases.   

There's almost an inverse relationship in Phase I and Phase IV in traditional monitoring, versus triggered and remote hybrid models. 

Phase IV studies are very well suited for non-traditional monitoring models. The industry recognizes that traditional monitoring is very expensive for longer, larger studies, and other options are needed.

Phase I studies are not currently the place for non-traditional monitoring models to secure their foothold. Given the relatively low number of sites and volunteers/patients, the opportunity for efficiencies may be modest.

Remote/centralized monitoring becomes a lot more "suitable" in the minds of respondents when it is combined with another model.

Triggered monitoring (and hybrid triggered-traditional) is viewed as very well suited for Phase IIIb studies.

Using a mixed model for monitoring is appealing to respondents and is, in fact, viewed as more suitable in some instances. 

Dyer agrees there's no one-approach-fits-all methodology: "No single monitoring approach can be used for all clinical trials. A clinical monitoring plan should be tailored to the specific human protection and data integrity risks of the trial and should also focus on the critical data and processes identified by the risk assessment."   

Clearly, survey respondents see the need for change and are open to it in the proper context. Because data quality concerns are the biggest barrier to adoption for non-traditional monitoring models, if they are to succeed, they will need to first and foremost ensure data quality does not suffer.  

"At Aptiv Solutions," offers Birch, "we have changed the data cleaning process such that study data is continually cleaned and reviewed in stream, and in parallel, by the combined team efforts of the data manager, programer, statistician, and medical (physician) reviewer. This ongoing data review by a physician ensures that the data is medically plausible and in a state that is ready for interim analysis at all times. Our 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. This includes the coding of all relevant data as well as undertaking the SAE and external data reconciliations resulting in data that are as clean as possible for making the adaptation decision." 

What can sponsors and CROs do to get ahead of the curve? 

A short leap of faith is needed. Help service providers put air-tight plans in place when it comes to data quality and patient safety. Increasing the penetration of non-traditional monitoring might end up costing more in terms of both hard dollars and soft oversight dollars (people's time). Look at this as an investment. Sponsors will also need internal advocates who are passionate about these models and who are influential enough to help garner support. Houston adds, "We've achieved significant savings from the classic CRA responsible-for-all-site-activities model by transferring site management, clinical data review/cleaning and data trend response to workers that excel with these specific skills and have a lower cost than CRA's.  Both the transfer of these responsibilities to centralized personnel at a lower cost per hour and the greater efficiency of the CRA at the site have reduced our overall monitoring costs significantly." 

 Coming to the table with a lot more trial planning, contingency, and scenario-based strategies for any trial involving a non-traditional monitoring plan is a necessity. Technology platforms and portals must be solid and near real time. From a marketing perspective, CROs must quickly develop named case studies that contain hard metrics. And maybe, most importantly, find some early adopters with whom to partner.  

Research showed no difference in respondents' interest in the monitoring models based on their company size. The study had hypothesized that mid-size and smaller companies would be more interested in non-traditional models, but this was not the case. Finally, the models must be cost effective for the sponsors. 

While the study examined various preferences for pricing models, (per patient, per site visit, fixed price/lump sum, fixed price per site that enrolls patients, price per CRF page, and hourly rate), respondents held varying views on which are preferred. 

Service providers will have options for how they plan to charge for these newer models, however some sponsors are leaning toward models that include a fixed-price component. This opens up the possibility for greater risk-reward contracts, and while those come with the opportunity for more profit, they also come with more volatility that could negatively impact cash flows. 

Current commercial forces are working to accelerate the adoption of adaptive monitoring designs.