Affecting Real Change

Applied Clinical Trials has been publishing articles based on solutions to the tightly regulated and highly competitive clinical trials industry for the past 20 years—the legacy of the industry is now being faced.

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You are probably well aware of the stats that underpin many of the articles, news stories, and presentations surrounding the clinical trials industry specifically, and drug development in general. For instance, how much is the cost of clinical trial delay is to a pharmaceutical company ($600,000 to $8 million). The average per patient cost in a Phase III trial for one year ($28,500). How much Phase III work is outsourced to CROs and service providers (54%). How much of a clinical trial budget is spent on subject recruitment (32%). What is the likelihood that a drug will reach the market from an IND (1 in 5,000). Taken separately, the stats drift around as big numbers. Taken together, what they mean is an unsustainable situation.

In response to its own challenges in the lack of pipeline drugs for development and loss of revenue from drugs coming off patent, pharmaceutical companies have turned to mergers, acquisitions, cutting jobs, and outsourcing. In response to that, CROs are trying to become more proactive partners to its clients as both move from transactional to functional alliances.

Each of these statistics and developments has its own list of sub-challenges as well as proponents for change. Minor change or systemic change within the industry is needed. And it is in this industry backdrop that late last month, 25 leaders from the clinical development operations sector convened in a private roundtable to discuss current major issues affecting their business. The Linking Leaders roundtable,* held quarterly with this being the fifth such gathering for the clin ops sector, took up the following topics in a day-long open dialogue:

• The effect of changing sponsor-provider partnerships

• How the increase in outsourcing has effected sponsor oversight responsibilities

• Risk-based monitoring

• Improving site performance through site management

To get some insight into the roundtable, Applied Clinical Trials interviewed four participants prior to the event. We uncovered some great ideas for small changes, as well as those that would mean change to the whole system.

CROs and sponsor relationships

"For me, the most interesting is the topic around building partnerships with external vendors and CROs," said Andrew Lee, Deputy Head of Clinical Sciences and Operations at Sanofi. "This is a major trend in the industry. We're all going down this path of selecting preferred providers and taking that from a provider sort of relationship into a strategic partnership. So it's an evolution and it's taking up a lot of resources and new modeling in the industry." While Lee says that this topic has been discussed at this venue before, as well as many others, there are certain components that need to be addressed. First, the mechanical component that requires shifting resources from within large organizations into a flexible or variable resourcing model with external partners. Lee says that this is a fundamental but not trivial event because "managing human capital transfers is not easy."

The second component is behavioral and includes three other segments:

• Does the partner have the expected capabilities, such as geographic spread, skill, expertise, and competence?

• How do you build an alliance to achieve a win/win relationship?

• How do you extract a value that is valuable for the sponsor as well as the CRO or vendor?

In that value exchange, Lee says, "We're looking at that from both sides. So the CROs are looking for that and so are the sponsors. And the Holy Grail is how do we make this more valuable and see that our investment returns more than if we did this alone?"

In the end, Lee believes that none of the relationships that are formed between sponsors or CROs are inherently difficult if you have trust and understanding.

Risk-based monitoring

For Mitchell Katz, PhD, Executive Director, Medical Research Operations at Purdue Pharma, risk-based monitoring is a key discussion. "That's an area that is really new to the industry. People are not really sure how to approach it—from their perspective, what's the right balance? And how to have a hands-off approach, yet stay involved in the program. Also, how to look at information and take advantage of the technology that might be available for us to continuously look at the data and the quality of data at these investigational sites."

For decades, most sponsors have conducted on-site monitoring visits every six to eight weeks with the goal of 100% source document verification, for all of the data, on all of the subjects. In its guidance document released in August 2011, the FDA put forth its thoughts on risk-based monitoring as a way to create a monitoring plan, as well as determining centralized monitoring over on-site monitoring needs. As far as the hesitancy of industry toward adopting a risk-based monitoring approach because of FDA concerns, Katz believes this guidance is an opportunity for industry to make a change.

Said Katz, "Historically, we always looked at monitoring as something you had to do on a routine interval for any program. And it's extremely costly. Yet it's known that the increased frequency in monitoring doesn't necessarily deliver better quality. So how do we manage quality in such a way where we're not separating ourselves from the study, but we're intimately involved in the nature of the patient information that we're capturing?"

Katz views this discussion as an opportunity for industry to standardize approaches by leveraging each other's experience and expertise as organizations.

"Individually, our organizations are very used to the old way and change doesn't come easy within organizations' leadership. People who experience successes are okay with doing it the old way. And what we need to do is introduce change," said Katz.

Managing site performance

Craig Wozniak, Head Americas Region, Clinical Operations, at GlaxoSmithKline, is focused on how sponsors can help sites be more productive and drive better quality. "I think it's important for us to share what our approaches are for site selection, qualification, training. Are there some new models or methods that people are using to try to improve that?"

But aside from sharing and having site representatives at the roundtable to offer a different perspective, Wozniak is a firm believer in the need to look inwardly. "We have to look at what we're designing in terms of protocol, materials, instructions. If you hand somebody something that's not simple or not clear, then it doesn't set it up for success," said Wozniak.

Unlike an area of clinical operations that has a specific regulatory piece around it like risk-based monitoring, improving the site management and productivity is an ongoing process, explained Wozniak, one that may not necessarily be unique and is related to the dynamics of conducting research. One example would be engaging with investigators, which is done continuously, and on a global basis. In this way, the processes are similar, such as making sure to take into consideration their regional differences or cultural norms. Said Wozniak, "It's not something that there will be a start and an end. I think there's a totality of looking at the opportunity that needs to be done."

Big change around big data

As one of the few CRO participants in the roundtable, Adrian McKemey, PhD, Managing Director, The Consulting Group at Quintiles, offered a different perspective not only because he is with a CRO, but because he spent many years at Boston Consulting Group. And as McKemey explained to Applied Clinical Trials, his position in Quintiles' consulting is to help sponsors see what the next model is going to be beyond the current CRO model. He gives advice to help sponsors anticipate and adapt to the future, which is very separate from the clinical operations arm.

So for McKemey, the connections between the major topics covered at the roundtable and what it means to the clinical trials industry is most interesting. He said he looks at this meeting as "a grassroots movement to dispense with much of the idiosyncratic behavior across companies that's getting in the way of being more efficient." And to do that, one has to look at the big picture, or in McKemey's words, big data.

"What makes all of these topics—pressing the reset button on monitoring; pressing the reset button on regulatory oversight; pressing the reset button on investigators, or on how one handles one's relationship to CROs—the common theme that makes all of those conversations possible is data," said McKemey.

In comparison to other industries that have already tackled the big data issue in previous years, such as financial services or consumer packaged goods, is that biopharmaceutical operations hasn't looked for the cumulative intelligence across companies, geographies, or phases to get to the next stage. Said McKemey, "Although few could exceed [biopharma's] excellence on the science and biostatistic side, we do everything in a very anecdotal kind of way. Whether it's choosing investigators or a CRO partner, deciding how to represent what we're doing to the agency, everything is created de novo."

To that observation, the two current changes that will be leveraged are: real standards being applied to data which allows all these disparate silo sources of data to be conformed and looked at in aggregate for pattern recognition and trending across them; and the grid or cloud computing approaches that are being applied to big and complicated data.

To relate this data to a topic at the roundtable, McKemey chose the site, and specifically, investigators. Institutions and CROs have used investigators as a proprietary and competitive advantage. "Turns out when you actually do the analysis—all the sponsors are working with the same investigators. There are very few who are unique to one particular company."

Because of this and the lack of standardized data, McKemey says that when a sponsor looks at a particular investigator set or when they're trying to find them, they're missing out on 90% of the experience that the industry has with an investigator. "And that just gives you a massive liability because that's the person who's going to recruit your patients, it's a person that's going to keep your trial on time, it's a person that's going to decide how clean your data is, and we're selecting them with very partial intelligence," says McKemey.

For McKemey, the solution is obvious. Take the so-called competitive advantage out of the picture. "Let's not see it as a competitive advantage. Let's see, in fact, it being a disadvantage that we're not sharing our cumulative experience. Let's put all of that information in one place."

Not only would the elimination of this de rigeur competitive advantage change the industry through the sharing of big data, but the working together to streamline and or standardize the practice of clinical trials could eliminate costs and truly re-invent the industry. McKemey uses the airline industry as an example.

"Last time you got on an airplane, you went through security and, got onto the plane and the pilot was there clicking switches above the cockpit console. And you probably would be hard-pressed to remember which airline it was because they have conformed everything it takes to get on a plane and be stewarded to a destination by a pilot. And they're competing on something different. They're competing on routes or they're competing on frills, but they're not competing on the basics. They've stripped all of that and said, "Let's make it all the same. Let's share all of that infrastructure."

In comparison, the biopharma industry is not conformed. Says McKemey, "When you start a journey of a patient going into a trial, you know, being taken on that journey by an investigator who's looking after their passage, it's different every single time. The way sites are selected, the way the patients get enrolled—so much of the process is done in a particularly unique, bespoken, customized way that needn't be." And these unique ways impose a lot of time and money into the system. "Every single way of engaging a biopharma company is different. It's exhausting," says McKemey.

And in particular to the investigator issue, with the well-known decline in the number of investigators engaged in clinical research contrasted to the increase in requirements from the industry, McKemey says is a recipe for disaster. The investigators are a shared, highly specialized resource on which everyone relies but nobody has accountability to sustain. And that, says McKemey is destroying the resource. However, he does see that changing in the near-term. Through discussion at roundtables, as well as creating pre-competitive alliances around investigators, and using the big data to have a cross-company perspective on the entire global investigator population, will offer a window into the capabilities; as well as performance. "And for those that are performing in the bottom quartile, they'll be able to make investments to increase sustainability of those researchers staying involved with developing new medicines. Because it's a finite population. You can't afford to have the massive churn rate of investigators at the moment to find a way to sustain those and a good potential but find the economics or the process too confusing."

As these clinical development operations executives noted, meetings like these facilitate solutions and keeping on top of industry trends. As Lee said, "I think we've all realized that operational excellence is not an issue of intellectual property. This is something we all struggle with. And if we work together to solve the problems, we have a much better shot at being better as an industry. Our industry is under pressure. It's not our companies. We're all under intense stress. So if we work together to solve these problems, we have a much better shot at solutions."

For more discussion with Andy Lee on these current operational challenges, register for our free live webcast "Top of Mind for Clinical Development Operations" on Wednesday May 23, and on-demand after that, www.appliedclinicaltrialsonline.com/mind.

*Editor's Note: The Editors of Applied Clinical Trials would like to thank Lesly Atlas and Pam Sobotka, the founders of Linking Leaders, for allowing us access to interview members of their Clinical Operations Roundtable. This network provides clinical trials executives with a unique interface to share insights and experiences, benchmark progress, and collaborate on solutions among a group of influential peers facing shared industry obstacles. Their boardroom-style roundtables, hosted on a quarterly basis, offer participants exclusive access to the latest thinking and full-day, intensive networking and idea exchange. Atlas and Sobotka have over 20 years combined experience in collaborating with senior-level clinical development operations, outsourcing, quality and CRO executives to develop industry-leading educational and networking meetings.

Lisa Henderson, is Editor-in-Chief of Applied Clinical Trials, e-mail: lhenderson@advanstar.com.