Laurie Halloran

	Life science executives who run and fund the most innovative companies are seen as bold leaders who seek to change the world for the sickest patients who could potentially benefit from their yet unproven therapies. However, press releases touting the record-breaking amount of capital raised to move products into clinical trials to confirm their benefits pay little recognition to the complexity of making those trials happen. 

	Halloran’s exclusive Clinical Operations Retreat for Executives, held this October on Cape Cod, convened 75 executives from medical device and pharma companies of all sizes working on a variety of products. A few vendors were hand-picked and invited to contribute their support to the conference. Discussion topics focused on the “devil in the details” of conducting challenging and complicated clinical studies in products that are in the news all the time as “game changing” and “at the forefront of innovation”. There was candid and collaborative roundtable discussion about several major considerations in both the design and the execution of these programs. We will summarize below: 

	It is critical to be mindful of study design for confirmatory studies because the tendency is to try to ask every possible question in order to maximize chances to detect signals of effectiveness.
	It is also an undeniably important medical need to carefully assess product safety as diligently and frequently as possible in the sickest of patients. Additionally, it is common for confirmatory studies to have protocols that are difficult to implement. Even so, physicians and advisors frequently add even more complexity, which often goes unrecognized prospectively and poses a tremendous burden of time and cost on patients and caregivers. 

	A key theme that emerged from the discussion was our colleagues’ effort to involve patients and research sites early in the trial design process to prospectively and critically assess the patient impact of the protocol’s procedures and visits as a way to identify ways to be more patient centric. Senior leaders often push back on patient-centricity initiatives due to the time and money involved. Notably, FDA recognizes the value real patient input brings to trial design, therefore the Agency is currently developing Patient Focused Drug Development guidelines-evidence enough that we in industry should jump on board.

	Some of the ideas about patient-centric design that emerged from the discussion are now becoming more feasible. There were strong suggestions to consider telemedicine and virtual visits, which will increase retention. One company accessed patients directly, while another brought the research sites’ study coordinators together to hold a focus group discussion centered on learnings from prior studies. Another idea was to identify a research center with the capacity to conduct a high number of gene therapy trials and formally engage the key team members in consulting on study execution. 

How could we better execute complex trials? 

	With any research site, comprehensive training on the study is key. However, with the elevated complexity of gene and cell therapy programs, site personnel are nervous and may not have robust processes in place to quell their apprehension. Thus, training is a factor that must be assessed prior to site selection. Several of our leaders felt that this was an important step for the biopharma company to conduct themselves, rather than one to delegate to a CRO. 

	Another suggestion that generated enthusiasm among our colleagues was to consider engaging veteran study coordinators in mentoring roles to guide new coordinators through the complexity of these studies. The industry is seeing unprecedented coordinator attrition due to burnout, so it is critical that leaders invest in training thorough enough to empower these key employees and foster job satisfaction. There is no one-size-fits-all coordinator training method, but it is universally important for senior clinical research leaders to recognize and budget for 12-months of new-hire ramp-up.

This is a great time to initiate a mentoring relationship. 

	Of course, it is imperative to create clear boundaries for this type of arrangement, and sponsors need to monitor the communication exchange and support mentors by ensuring the information they provide to mentees is accurate and does not introduce medical or safety concerns. Identifying the best mentors and providing compensation is another administrative burden that can ultimately optimize study conduct, but also brings a variety of challenges around timing and administration. Consideration of these obstacles should be done during protocol development so that expertise is leveraged early enough to make a difference in the final protocol design. 

	This is not an exercise in cost-cutting; the procedures and treatments still have to be executed and delivered. Optimizing trial design using creative approaches and thoughtful re-structuring is simply a way to get more for the money we invest in bringing life-saving therapies to patients in need. It is critical that we adapt our strategies in concert with the increasing complexity of disease. 

http://www.clinicalinformaticsnews.com/2019/01/09/starting-line-how-to-begin-getting-patient-input-into- clinical-trial-design.aspx

https://www.clinicalleader.com/doc/is-there-a-solution-to-the-cra-shortage-problem-0001

Articles

Insights from a roundtable at Halloran’s Clinical Operations Retreat for Executives covering major topics in both clinical design and execution.

Laurie Halloran

Articles

Operationalizing Complex Clinical Trials