Evaluating Challenges to Clinical Trial Execution

Industry Snapshot – Clinical Research

Our industry has had an impressive history of blockbuster drugs, life saving medicines and new therapies that have enhanced the lives of many. Currently, our industry is facing challenges that have caused drug development costs and timelines to increase at alarming rates. As a point of comparison, in the 1960s, a new drug could be developed in 8.1 years; by the 1990s it was taking over 15 years [1]. While the industry has seen a drastic rise in the time to develop drugs, expenses have gone through an even more staggering increase. Over the past 40 years, the cost of drug development has escalated from a mere $4 million in 1962 to an astounding $800 million or more, in today’s market [2]. In 2001, research and development spending hit $30.5 billion [3], grown to an estimated $51.3 billion [4] in 2005, and is expected by some to exceed $105 billion by 2010 [5].

There will continue to be challenges and delays during drug discovery, preclinical testing, and clinical research that are simply unforeseen and uncontrollable. Particular to clinical research, these industry norms also present a greater opportunity for sponsors to evaluate better ways to optimize productivity and mitigate risk. Many sponsors have discovered that the answer does not lie within their own organization, but rather in the innovation and services of another. Unique management models, new technologies, and creative study approaches can combat the increasing timelines and costs of clinical research. By taking a closer look at the categories of Study Planning, Site Productivity Evaluation and Recruitment, disconnects are uncovered in project management and identify where innovative approaches could provide impact. Ultimately, questions still need to be addressed. How will drug development sponsors embrace a new approach that can optimize site productivity and mitigate risk? What are the right ways to incorporate a novel approach into your next study design?

Opportunity for Improvement
Industry reports claim that Phase I-IV clinical research accounts for over 35% of a drug’s development cost and continues to be the source of some of the most painstaking delays [6]. Sponsors are in a constant search for ways to reduce these delays, now accepted as an industry norm for these phases of drug development.

Recently, technology innovation has streamlined data entry and case report forms into an electronic format that delivers greater consistency and quality than the previous paper-based reporting. The introduction of EDC offers sponsors and CROs an alternative that saves time without sacrificing quality and allows for more efficient and effective monitoring. DataLabs reports that EDC allows the rapid cleaning of patient data, which can accelerate a clinical trial by reducing the time to lock a database by 60% or more [7]. These benefits and the ability to be easily incorporated into a study or organization have led to an adoption rate for clinical E-technologies of 35% based on a 2006 survey [8]. A slow adoption rate raises questions: Is the benefit not worth the time, the effort, the cost? Or is it not being adopted properly? Looking beyond the scope of technology to innovation at a logistics and operational level, Accelovance, a clinical services provider for Phase I-IV outpatient research, offers clients more control over the quality, speed and cost through an offering of integrated services.

Accelovance has focused its efforts on implementing an operational model that drives high subject throughput over a short period of time by optimizing subject recruitment and site productivity. The company also manages monitoring schedules and data output so that all efficiencies are realized. This model does not apply to all therapeutic areas, nor is it designed to, but does cater to studies where subjects can be recruited from the general public. As it accomplishes these objectives for this niche market, the operational model may set the tone for similar management of other therapeutic areas as well. How can a single company optimize site productivity after struggling for decades? Integrated services supported by ownership, control and dedication. Unlike any other services group, Accelovance has uniquely positioned its wholly owned/operated sites with centralized subject recruitment and standard CRO services including data management and monitoring. From a resources perspective, “wholly owned/operated” translates into: optimizing site productivity due to research dedicated PIs and CRCs; controlling site operations and dedicating capacity to a specific study; utilizing a recruitment budget efficiently; driving high subject throughput; and managing data output. Compare this model to what dominates the clinical research industry: disengaged PIs and limited CRC support; substandard site operations; inefficient utilization of central recruitment; poor subject recruitment and retention; unproductive monitoring schedules/visits. This may pose the question: How often are the sponsor’s goals compromised by those executing the study?

Where the Breakdown Begins
According to Applied Clinical Trials (ACT), 86% of trials experience delays [9]. In 2003, CenterWatch reported 94% of studies saw a delay of over one month [10]. Regardless of a study sponsor’s size or presence in the market, a delay of this length will have an impact on multiple fronts. Site selection, subject recruitment, site operations, monitoring, data processing – all of these are separate functions that require multiple partners. Even with only two or three separate groups, there is a disconnect between study goals, site execution and project management. To explore this further, each of the factors of Planning, Productivity at the Site, and Recruitment will be examined.

Planning
A sponsor’s planning efforts can be compromised by their dependency on, and the uncertainty of, a site’s ability to meet study obligations. It is well known that inconsistent recruitment across sites leads to initial study delays, but also has an impact when looking to monitoring visits and data output. Study planning can be enhanced with greater control which helps mitigate the anticipated delays around study start up, subject recruitment, monitoring and data collection. Recognizing the short comings of how individual sites function, an integrated network following Accelovance’s approach puts a study in a better position for success. Experience has shown that typically the date enrollment begins and the date recruitment begins is one in the same. By proactively planning for the study and predicting enrollment milestones, Accelovance can also properly schedule monitor visits to optimize data collection and output to the sponsor. This is accomplished by identifying capacity, personnel, resource, and timing issues as well as implementing recruitment strategies prior to enrollment start. Sponsors now have a more effective way of planning for all staging that can give them confidence in their study timelines, from recruitment to data lock.

Productivity at the Site
Much of the disconnect between the different components of study execution begins during a sponsor’s evaluation of a site’s true ability to meet study objectives. As observed with studies seeking healthy subjects, site qualification is based on the following: past experience; reputation of the PI; size of patient databases; and locations for travel and monitoring. Despite meeting such qualification criteria, individually operated sites still have trouble achieving enrollment goals, meeting retention expectations and preparing enough data for monitor visits. Unfortunately, sponsors are almost forced to settle for sites and PIs promising one thing but delivering another. Would a research dedicated staff, allocated capacity and control over site operations help overcome these obstacles? The industry has seen unprecedented value in having both CRCs and PIs committed to clinical research and the study at hand. Accelovance recognizes the key way to deliver high subject throughput for a site, while increasing quality and maximizing data output, is to incorporate world-class coordinators and research focused PIs into its operational model. The end result allows the personnel at each site being fully focused on the study, ultimately delivering value in terms of quality, speed and cost.

The Recruitment
Looking to the common recruitment efforts at the sponsor and site level, patient databases are actually quite an ineffective way to rely on meeting enrollment figures. The Institute of Medicine states that 30% of clinical trial participants report they first learned about a trial from their primary health provider and that most information comes from media or the internet3. If this is true, how can a sponsor or CRO expect its sites to recruit 100% of its subjects from PI databases? Even with the help of a recruitment agency, there still is little guarantee that this will be a solution. Why? The lack of control and integration of services. A strong media campaign may be implemented; but how is site feedback obtained if each site in a study operates independently? Are sites prepared to take advantage of a mass media campaign? Could they, or do they want to, handle the high call volume? Successful recruitment campaigns combine management of media placement, real time response monitoring and control over site operations, and matching high call volumes with high subject throughput. This allows for real-time evaluations of which specific media is leading to randomizations, at what rate and at what cost. Sponsors who have made an initial investment in recruitment at Accelovance sites have seen trials enroll much quicker than expected and have actually saved money by not having to add rescue sites and extend enrollment periods.

Imagine an organization that combines site ownership with proactive recruitment and full CRO services. The result: sites that optimize productivity, handle high subject throughput, meet enrollment objectives and maintain high retention rates, and save the sponsor time and money. This is an example of innovation in the marketplace and how a company is working to redefine the term “industry standard.”

Embracing a New Approach
There are a range of challenges that sponsors and CROs continue to encounter, with little ability to change or develop greater predictability for clinical studies. Instead, sponsors should explore and consider new approaches that take the strength of site ownership and operational control paired with proactive subject recruitment resulting in higher throughput studies in less time. EDC is an example of time and cost saving technology with a slow adoption rate. There are ways for companies large and small to accelerate implementation of ideas; to mitigate risks and validate the true value and potential of a new approach. Here are a few thoughts:

Expand a drug development company’s R&D budget to include the investigation of new approaches, not just technologies, which may save the company time and money. Much like the sponsors viewed EDC and IVRS as ways to drive higher quality and reduce costs, research on an integrated services approach may reveal cost savings, higher quality and most importantly, save time in the clinical phases of research. If an innovative approach can offer this, then it can also combat a growing trend of constant trial delays, which can cost a company up to $8 million each day their product is not on the market [11].

Understanding that sometimes it may be hard for sponsors to adapt new technologies, some approaches use a set of integrated processes that do not require “new” technology. A sponsor must be careful not to impede the true capability of the new process by suffocating it within already existing systems. In order to realize these benefits, a sponsor must be open minded and willing to work within the parameters of the innovative approach, not imposing traditional ways of operation. Likewise, not using enough of the approach may actually prevent the sponsor from realizing the true value it may deliver. As an alternative, sponsors could view an innovative approach as an opportunity to test low priority programs or a sample of a larger program. Embracing a new approach in this manner mitigates risk, yet maximizes the initial investment, and allows sponsors to experience the benefits on a scale more acceptable to them.

Accelovance is an example of a company with a unique approach to addressing many of the industry’s concerns and growing challenges. A select number of highly efficient, research dedicated, and centrally managed sites with proactive recruitment can deliver higher quality data in a shorter amount of time. But how will a company embrace such a dynamic and unique approach? Can it be sampled on a smaller, yet representative scale to influence future decisions? Or will companies find themselves content with inefficient sites? Longer recruitment periods? Dependence on PI databases and recruitment agencies that still will not achieve enrollment objectives? There are companies who recognize the need for a radical change to internally challenge what has become accepted by others as standard in the industry. Are you one of them?

References

1. “Facts and Figures,” Center for Information and Study on Clinical Research Participation, 2004.
   
2. “Drug Development: The Short Story: Cost of Drug Development,” Network Science, 1995-2006.
   
3. “101 Facts about Clinical Research,” The Center for Information and Study on Clinical Research Participation, July 2005.
   
4. Burrill & Company, Pharmaceutical Research and Manufacturers of America (PhRMA), 2006.
   
5. “Global Contract Drug Development Spending to Reach $42 Billion by 2010,” Genetic Engineering News, May 2005.
   
6. Crowner, Robert, “Drug Pricing vs. Drug Development,” Action Institute for the Study of Religion and Liberty, May 2002.
   
7. Data Labs, Inc., June 2004.
   
8. Connor, Chris, “Has EDC Jumped the Shark?,” IDC Health Industry Insights, July 2006.
   
9. Canavan, Carl, “Integrating Recruitment into eHealth Patient Records,” Applied Clinical Trials, June 2006.
   
10. Weinberg, Myrl, “Engaging the Public in Clinical Research,” Regulatory Affairs Focus, July 2006.
    
11. Beasley, Donna, “Recruiting Special Patient Populations,” Applied Clinical Trials, June 2006
    

About Accelovance

Accelovance, Inc., based in Rockville, MD, is a CRO specializing in high patient throughput from recruitment through study completion. Accelovance has developed a model to increase the reliability and productivity on Phase I (outpatient) and Phase II-IV trials. Each study is approached with the intent to complete enrollment BEFORE the study starts. With critical planning and full control of CRO services, central patient recruitment, and ownership of clinical sites, Accelovance is committed to delivering high quality, predictable, and cost effective clinical trials.