By Deborah Borfitz 

February 10, 2023 | At this week’s Summit for Clinical Ops Executives, Genentech’s Virginia Nido delivered a call to action to her industry peers, asking them to learn the landscape of collaboratively developed clinical trials solutions and start using them. “These solutions are available to us right now, mostly for free, across every phase of the drug development life cycle,” she says. 

Nido serves her company as global head of product development industry collaborations and a decade ago worked on the TransCelerate Common Protocol Template team, which helped sharpen her bold vision for the future. Such “wisdom of the crowd” solutions, even when created with the best available subject matter experts, can be met with “a lot of hubris and arrogance,” she notes. “We had workstream members who truly thought their protocol template was the best in the business and somehow they were getting drugs approved because they had a good data management section.” 

As she covered in some detail, clinical trials have gotten better over the past 20 years because patients have a better shot of being in one, more therapies have a companion biomarker, and sponsors have worked hard to make studies more patient-friendly. “But we now need to take it further,” she says, speaking to a room that included senior leaders having the power and “ethical imperative” to make trials the best they can be for every patient. 

But she began with a personal story. Two decades ago, the then-pregnant Nido got the dreaded phone call that her mother’s ovarian cancer was no longer responding to treatment, and she would need small bowel resection surgery and an enteral feeding tube. Even then, her mother wasn’t expected to live more than a few more months. 

She held on for a full year—in part, Nido believes, because she wanted to meet her first granddaughter. “My mother was never on a clinical trial and that was not for lack of trying... there were no trials that [she] was eligible for [at the time].”  

Whether anyone in the audience would want to put their mother in a clinical trial today would have a lot of dependencies, continues Nido, such as whether she has a life-threatening illness or chronic condition that is relatively well controlled by the standard of care. They would likely have lots of questions and would want to see the study protocol and informed consent documents as well as know how many blood draws and clinic visits were involved and how many of them could be done remotely, and if the randomization scheme would give their mom a chance of being on the active arm at any point during the trial. 

How is industry doing creating well-designed, high-quality trials with “clinical equipoise,” she rhetorically asks, meaning not overly burdensome and with meaningful endpoints? Not as bad as many “gloom-and-doom articles” suggest. A movement toward collaboration has been building over the 20 years that is leading to better quality clinical trials for potentially everyone. 

Better Trials 

Evidence supporting Nido’s argument that trials have improved includes the fact that there are more of them today than in 2000 at the inception of ClinicalTrials.gov—a little over 1,000 then versus more than 400,000 as of January 2023. While no trials were available to her mom back then, 58 phase 3 studies for ovarian cancer are currently registered.  

At the same time, thanks to advances in precision medicine, trials are doing a better job of pre-selecting patients with companion biomarkers so they can have better potential success on a new therapy, she says. Biomarker-driven trials have more than double the chance of being successful from phase 1 through approval across all disease areas, relative to those not using any. 

During the 1980s AIDS pandemic, patients and their caregivers jumpstarted efforts to make trials more patient-friendly with the creation of Act Up (AIDS Coalition to Unleash Power) to demand access to investigative therapies, says Nido. This was followed by patients who launched Breast Cancer Action to demand access to novel monoclonal antibody therapy, and groups such as the Cystic Fibrosis Foundation, the Michael J. Fox Foundation (Parkinson’s disease research), and PCORI (Patient-Centered Outcomes Research Institute) in the U.S. and the Patients' and Consumers' Working Party (PCWP), Patient Focused Medicines Development (PFMD), and the European Patients’ Academy on Therapeutic Innovation (EUPATI) in Europe. 

“These groups are getting a stage... a voice, and sponsors are starting to listen,” says Nido. While they are responsible for many important advances, much remains to be done to improve clinical trials.  

Abundant Resources 

The formation of the Clinical Data Interchange Standards Consortium (CDISC) in 1997 can be thought of as “the roots of a growing tree of industry collaborations,” Nido says. That’s when data scientists from competing companies decided to stop talking about their data challenges at conferences and instead come together as peers to start creating standards for the collection and curation of clinical trial data for registrational purposes. 

CDISC was followed in 2004 by PHUSE (Pharmaceutical Users Software Exchange) and the 2007 creation of the Clinical Trials Transformation Initiative (CTTI), a public-private partnership facilitated by the U.S. Food and Drug Administration (FDA) where “everyone, but especially patients, were invited to the table,” Nido continues. 

Meanwhile, the EU government and EFPIA (European Federation of Pharmaceutical Industries and Associations) in 2008 created the public-private Innovative Medicines Initiative (IMI), “the largest health initiative in Europe,” she says. The following year saw the launch of Harvard’s Multi-Regional Clinical Trials (MRCT) and, in 2012, the Society for Clinical Research Sites (SCRS), focused exclusively on giving sites a voice in the industry, and TransCelerate, “dedicated to tackling the toughest and most persistent challenges in drug development.” 

Collaborations focused on more specific challenges arose next, among them GA4GH (Global Alliance for Genomics and Health) in 2013 and, in 2020, the Decentralized Trials and Research Alliance; the Digital Medicines Society (DiME); Vulcan Accelerator, dedicated to closing the gap between clinical care and clinical research; and Accumulus Synergy, creating a digital platform for real-time data exchange between sponsors and health authorities, she shares. 

In 2021, the Clinical Research Data Sharing Alliance (CRDSA) was established to focus on giving and getting post-trial data, adds Nido. In 2022, the Inter Company Quality Analytics (IMPALA) Consortium was born to promote the use of advanced analytics to build patient trust while accelerating drug approvals.  

These collaborations have been “creating, prolifically,” valuable clinical trial solutions and making them available on the web, Nido stresses. In terms of study planning, for example, CTTI has an abundance of resources around diversity and the development of novel endpoints. DiME offers a lot specific to the development of digital endpoints, and TransCelerate has a whole suite of tools that includes the common protocol template as well as common adverse event fields and common statistical analysis plan. 

In the realm of study startup, the offerings of the CTTI includes informed consent and investigator qualification and similar types of resources are available in Europe from the IMI. Harvard’s MRCT has a large toolkit on diversity plans, equity by design, and health literacy, Nido adds, and the assets of TransCelerate extend to forms for investigator sites and GCP mutual training recognition. 

For study conduct, the CTTI, IMI, and SCRS all have options for the picking, she says. TransCelerate can help companies modernize clinical trial conduct, based on lessons learned conducting trials during the pandemic that were turned into best practices. 

Trial closeout, analysis, and reporting resources are available from CTTI (ClinicalTrials.gov reporting), the CRDSA, MRCT, and TransCelerate (tools to anonymize and share post-trial data and for modernizing statistical analytics in a patient gratitude toolkit), says Nido. 

Change Agents 

Despite the bevy of available, mostly-free resources, trial sponsors often opt to continue doing things the “old way,” pass on the offers of help, or hire an expensive consulting firm to learn how other companies are handling various clinical trial challenges, Nido says. 

The reason, she quickly adds, is that adopting industry collaboration solutions is not all that easy. For starters, solution development takes a long time—in some cases, up to four years—and sponsors in the meantime “might develop their own solution is parallel.” 

In any organization but especially large ones, change is hard, Nido continues. “While you may be able to get a solution adopted in one part of the organization... [elsewhere] where you don’t have as much influence, [people] might just keep doing their own thing.” 

Based on work done by the Tufts Center for the Study of Drug Development, key change management obstacles include lack of senior management support, lack of cross-functional alignment, lack of regulatory clarity, and limited incentive to initiate, she reports. In the absence of a specific health authority mandate, for example, some sponsors might stick to the status quo—particularly if the new solution threatens someone’s professional identity or livelihood.  

In discussing how to remedy the situation, Nido says it is important to “remember you are playing the long game” and “stick with it” to see real change. “It’s a journey and you can’t really skip any steps along the way.” Senior leaders are advised to use their pull to adopt solutions that match their business priorities (e.g., real-world data or data-sharing). Some of the larger consortia, including TransCelerate and CTTI, have already done the return-on-investment analysis on companies’ behalf. 

“Use whatever argument works in your organization,” she says. “Is this likely to be a health authority mandate anyway? Consult with your regulatory colleagues; they know this landscape and they know what’s coming down the pike that is going to impact how you conduct clinical trials. Then find an industry collaboration solution that has already gotten ahead of this.” 

Nido specifically cites FDA guidance on diversity plans, which many of the consortia saw coming long ago. Subject matter experts working on any industry collaboration workstream can serve as the internal change champions for whenever implementation of a solution makes business sense.  

A highly underutilized approach, she says, is to “mobilize your global process owners, your SOP owners; they are our internal subject matter area experts. Let’s empower them to be our external experts. They should know this industry collaboration landscape and be able to pick and choose what works for your organization.”