Innovation In Clinical Trials: What Can We Expect In 2015 And Beyond?

By Ed Miseta, Chief Editor, Clinical Leader

Innovation is a critical topic in the pharmaceutical industry. It is what will help the industry keep on top of quality issues, develop new products, speed needed medicines to patients, and bring down the cost of the entire process. However, identifying where it can best happen and then making the vision a reality is also one of the toughest challenges that sponsors face.

I assembled a panel of some of the best innovative minds in the industry to discuss the trends happening in regard to innovation, and what we can expect to see change in the coming years. The panel included:

What are a few of the larger trends you are monitoring that could significantly impact clinical trials?

FRANCES GROTE: There are a number of trends that could potentially have a major impact on how we conduct clinical trials within the next few years. A few of these are fairly widely acknowledged, such as using a risk-based approach to monitoring and fully leveraging remote data capture, while others are in earlier stages of evaluation or adoption. Some of the key ones in this latter group are obtaining patient input into clinical trial design, maximizing site relationships with a core group of investigators, and various mechanisms to “virtualize” clinical trial conduct through the use of novel data collection modalities like wearable monitoring devices, apps, and use of EMR data. It’s exciting to see our industry becoming more open to realtime innovation, but we still have lots of opportunity to move the needle farther towards innovation.

CRAIG LIPSET: I continue to monitor the proliferation of digital tools (mobile, social, and health information technology), the increasing role of the patient as a participant in healthcare, and the changes in health delivery infrastructure from retail clinics to integrated health networks. Our innovation priorities for clinical trials are anchored around datadriven and structured protocols, making studies easier for investigators, improving clinical trial participant experience, and streamlining the capture of study data.

JEFF KASHER: Those are all good comments. I would add how effectively and consistently RBM is implemented across the industry (both within and outside the U.S.). We also have to consider the economics of clinical research. Early data I have seen indicates that clinical trials reduce an institution’s cost per patient and results in improved patient outcomes. Finally, wearable devices and patient-friendly ePRO apps will have a great impact on trials and patient recruitment/retention.

What do you feel will be the larger disruptors in the conduct of clinical trials in the next five years, and will the driving force tend to be sponsors or CROs?

KASHER: This ties in with the previous comments about the role of the patient. I believe the larger disruptions in the conduct of clinical trials in the next five years will be driven by neither sponsors nor CROs…it will be driven by the patients and research sites. Clinical research must become a “treatment option,” which means patients will have a large voice in the design/feasibility of trials. Patients, along with their physicians, will match to the trials in which they want to participate. They will discuss the trial, sponsor, and physician on social media and in patient groups, if they are not doing so already.

GROTE: In addition to the novel areas of trial conduct I mentioned above — and no doubt some we haven’t even envisioned yet — one of the greatest disruptive forces our acknowlindustry has ever seen is the magnitude of and interest in collaboration that’s arisen over the past few years. TransCelerate is an inspiring example of how we can create value without sacrificing competitive advantage. Recent inclusion of CROs in that collaboration via the ACRO forum points to how critical collaboration has become for continued success. We are rapidly approaching a time when the economics of developing drugs under our old competitive models will become prohibitive. But in an industry as large and diverse as ours, successful change fundamentally depends on having many parties buy into that change in a specific way that benefits all. That drive for collaboration is also seen in individual sponsor/ CRO relationships. With the volume of jobs shifting from sponsors to CROs over the past several years, there’s been a broad cross-fertilization of talent. Sponsors are rapidly discovering the benefits of relying on CROs for more strategic and value-add activities than in the past.

LIPSET: In addition to that, I would just add that over the next five years I expect to see radical changes in how clinical trial data is captured (eSource, voice-of-the-patient, proliferation of wearable technologies), as well as where trials are conducted (following the evolving health delivery landscape).

What areas are “blind spots” in pharma clinical research (areas that may create big impact but are not currently being addressed or pursued in earnest), and how can sponsors and CROs work together to address them?

LIPSET: That’s an interesting question. While we may leverage novel channels in an attempt to reach patients with information about clinical trials, we have a blind spot as to what happens when those patients bring that information to their treating physicians. Data is revealing how many patients wish to learn about research studies, but how few healthcare providers discuss research participation. Anecdotes from patients complement this data, in some instances with stories of physicians actively discouraging participation. Even the most effective message of a trial will be challenged if treating physicians fail to provide encouragement and support. Sponsors and CROs must develop strategies to better engage treating physicians and help to shed light on this important blind spot.

KASHER: We have seen slow uptake on developing multiple sponsor/molecule enduring protocols. Lung Map or iSPY are good examples of this approach. At the end of the day, the molecules which have the best risk to benefit ratio for a specific subpopulation of patients will be the winners. A protocol which can accommodate multiple molecules on an ongoing basis eliminates the repetitive identification and contracting with sites, training is streamlined, and patients can have a better chance of getting an efficacious molecule.

GROTE: Two significant “blind spots” immediately come to mind. One is that our industry continues to lag in maximizing the use of technology. As Craig mentioned earlier, I expect to see that change over the coming years. The other is our fairly universal resistance to acknowledging the realities of enrollment timing. Recent data from the Tufts Center for the Study of Drug Development confirms that across diverse therapeutic areas patient enrollment is consistently much slower than planned. There are a number of potential take-home messages from that, but standard process improvement methodologies clearly indicate that you can’t fix a problem if you’re not willing to “take it offline” and address it. For many companies the current approach is to continue to plan based on market forces or other goals unrelated to enrollment drivers, and then when problems arise, deal with them in a reactive or crisis management fashion. CRO input is key to gathering up-to-date industry intelligence, both when using technology and improving planning processes. CRO personnel tend to have broader exposure across a number of sponsors. While they can’t share confidential information, they do bring a wealth of operational expertise. The biggest challenge to getting the full benefit of that is within the CROs themselves as, from a sponsor perspective, they don’t always seem to have robust mechanisms for sharing knowledge within the CRO.

Collaboration between pharma companies and between pharma and CROs can enable innovation. Can you discuss when it is best to innovate together vs. when it is better to go it alone?

GROTE: I’m willing to take the first stab at that one. From my perspective, the question is not WHEN to innovate versus go it alone, but how and what to innovate. Innovation can arise from unexpected sources, and sponsors are not always well-positioned to quickly take advantage of that because they tend to have more rigid SOPs than CROs. Their internal decision-making and approval processes can also be longer and more labor-intensive to conduct. A robust process for making the most of innovation should allow for rapid evaluation based on clear business cases, empowered decision-making, and prioritization based on the ability to adequately support projects. Historically our industry has operated on the premise that CROs can contribute to operational innovation, but that scientific expertise is the domain of sponsors. Over the last decade we’ve seen some blurring of those distinctions, especially in the discovery space. But if sponsors and their CRO partners can implement truly effective processes for evaluating and acting on innovation, there’s no reason that novel ideas from any source can’t be acted on appropriately in a joint fashion.

LIPSET: I think Frances makes some really great points. An old proverb states if you want to go fast, go alone; if you want to go far, go together. The proliferation of collaborations today begins to violate this proverb — initiatives such as TransCelerate are bringing together highly motivated and like-minded peers across companies showing an ability to defy the rule that going together sacrifices speed. Collaboration is the new baseline, but we must continue to differentiate and challenge boundaries. The latter is where we continue to go it alone – the game-changing opportunities that require true leadership.

How can pharma companies better organize to support innovation in their organizations? Can you share a few best practices?

KASHER: In many organizations the innovation group seems to be decoupled from the molecule development teams. This creates a situation where every innovative pilot must be shopped to multiple teams in hopes of finding one who will agree to participate. Implementation of innovation requires an organization where the culture expects/encourages/desires that innovation is piloted and then scaled, if appropriate, on clinical trials being conducted by the molecule development teams. There is risk of failure, as exists for the molecule itself, but this must be done in a smart manner that protects patient safety and data integrity.

GROTE: Over the past few years our industry has seen a number of different models implemented that are geared to supporting innovation. What most of these seem to have in common is an underlying strategy of allowing a group of people to operate independently of the parent organization. Though different models vary on the level of support, number of personnel, strategic imperatives, and “distance” from the parent organization, it’s fascinating to me that all the models appear to have an underlying premise that innovation will happen better outside the sponsor’s walls. Potentially that speaks to some opportunities for change within the walls as well. At Biogen we have created a few different approaches to working innovatively — disease-specific innovation units that conduct clinical trials, scientific collaborations to conduct research, and a group focused on a value-based approach to meeting unmet medical needs. While the people working in these areas are empowered to focus on novel opportunities, these units remain an integral and fully integrated part of the larger development organization.

LIPSET: There are many models for large organizations to adopt to support innovation. Some may ring-fence and protect their innovation activities, while others may embed their innovation efforts deep inside their operations. My approach has been the latter — I feel it is too easy to test most anything in a protected sandbox. It is harder to make it work from within the operations, where colleagues will challenge new approaches at every step. But challenge makes the idea more robust and resilient, and ultimately more likely to succeed in the real world in bringing impact to the organization.

Ultimately organizations should not become enamored with ideas. Innovation is about the implementation of appropriate ideas to drive value in the organization. Ideas are often commodities — we all have ideas. The hard work is curating those ideas, implementation, and ultimately scaling what works. But that is how we will return value and make an impact in developing new medicines.

I also look for CRO partners to be aligned and transparent with regard to innovation. Where we can share priorities and goals, we can create opportunities to co-invest that are mutually beneficial. The alternative leaves innovation as just another transaction.

The most recent Pharmaceutical Outsourcing Monitor gave a tip of the hat to thought leaders like yourselves. But it also cautioned that we be careful to not overlook the innovative ideas that originate from the worker bees doing their jobs on a daily basis. How can a pharma company’s culture help to support innovation, and are there ways to better align the culture of the sponsor and CRO to support innovation?

LIPSET: That’s interesting. I had actually not seen that. I would say that I am very transparent about the source of good ideas – they don’t come from me! I sit inside the operations area at Pfizer and surround myself with the smartest people I can find at all levels both inside and outside the company. My work is to help them bring their ideas to life, with robust business cases and plans to scale where they succeed.

My goal in sharing examples of peers implementing disruptive new innovative approaches is not to champion one idea over another. I share these examples to inspire others and to show them how colleagues are driving to implementation and challenge us all to drive change.

I saw this impact first-hand as we shared our journey with the REMOTE trial. While some of the components worked and others did not, perhaps the greatest legacy of that project is the impact on colleagues inside and outside of my organization in believing that they are not constrained by the way we see our world today. If we all choose to be fast followers, then it’s a race to the back seat of the car with no one behind the wheel.

KASHER: Well said, Craig. I completely agree with that. If anyone thinks the innovative ideas originate from the “thought leaders,” they are sadly mistaken. The insight, ideas, and sanity checking largely come from people in the “trenches” at pharma, CROs, and research sites. To support innovation, a culture which fosters thinking differently must exist in the face of predominating pressure to go faster and deliver on “quarterly expectations of the street.” This is no different in pharma or CROs. Leadership which creates motivation and safety for folks to innovate is desperately needed across the industry.

GROTE: Biogen and our clinical development CRO partner, Quintiles, are jointly focused on how to foster and get the full value of the innovations that arise from the people doing the work. We are collaboratively sponsoring multiple programs to encourage individuals and teams to bring forward innovative ideas and have put a process in place that makes it easy and offers recognition for the “people on the ground” to bring forth suggestions and recommendations. While the formal program supporting this is relatively new, we’re already seeing great enthusiasm within both companies and a high level of responsiveness.