No Going Back
Exactly 10 years ago, the FDA’s Guidance on Industry Oversight of Clinical Investigations proposed a risk-based approach to monitoring. I spoke about it at a global meeting, excited there was a way to modify an extremely cumbersome process that yielded beneficial outcomes by taking a thoughtful risk-based approach. After my presentation, my mind was blown by one of the questions from a monitor. She asked, “What if I don’t pick up a side effect during my chart review and it turns out to be a trend that ultimately impacts the safety of the product for patients?”
To me, this view embodies the whole industry’s reluctance to let go. The monitor would never have diagnosed the trend – it was not her job. But she saw her role as the key detector of all things anomalous. She couldn’t recognize the time she’d spend (and the cost she’d incur) doing a 100% review of every single data point for one patient, a review that would never pick up a trend in a large double-blind study. We have since learned that the yield from this laborious effort is a negligible 2.4% improvement in data quality.1
Fast forward 10 years. I felt the same forces coming together when the world shut down due to COVID-19. I was filled with hope that there might be a chance to embrace the technology that has existed for years, but for a million different reasons, all under the headline of “risk aversion,” this has yet to become mainstream. Having every patient stuck at home, but still wanting and needing to continue in their clinical trials, offered an enormous opportunity for us as an industry to start to move forward and figure out a way to make it work.
My team immediately started to design an offering to support our life-science clients to adopt decentralized approaches for their ongoing trials so the subjects could continue. We also offered a weekly, panel-style town hall via Zoom to help our clients and colleagues learn from each other in real time, and at its peak, we had several hundred people collaborating to find a way through it together.
Now, a year later, we have learned a lot about what has worked and where the challenges remain. I’ll share a summary of the insights below because I think we should all be vowing to never go back.
Obstacles and Solutions Are Different Than They Appear
The first thing people think when they begin to consider a decentralized trial is fear – how will this be approved by regulatory authorities? But, in fact, the FDA is supportive of and advocating for this model. How sponsors will make their trial decentralized is now the source of focus, and it continues to generate anxiety in many colleagues. It can be very difficult to let go of the past and reimagine a new way of operating.
What we have learned is that decentralized trials are not a one size fits all, and they aren’t just at-home visits or telemedicine assessments. There is a need to systematically work through the protocol as a team and determine the changes that make sense and where technology solutions have shown a high degree of integration within the patient’s journey. Some companies have constructed a “choose-your-own-journey” protocol and, with careful documentation that manages risk and documents the rationale for their choices, have sailed through inspections without any findings related to protocol deviations.
Once a protocol is almost final, it’s important for the sponsor’s team to work with the FDA to determine how to obtain guidance and feedback to ensure they’re moving in the right direction until the methodologies and operationalization have become more mainstream. The simple advice we must accept is to take that input from the FDA to engage with the HA (type C meeting request). We have learned that the FDA is welcoming of this because it gives them insight into sponsor activity.
The FDA is interested in sponsors’ tactical processes and use of technology to obtain consent and collect data, but it’s important to work through the protocol to sort out the potential areas that may be a challenge. Many protocols have way too many procedures and collection of “nice-to-have” data, so this is often the hardest step with a team who has trouble letting go. But if you have kept the safety assessments as the top priority and have options for easing the patient journey through technology solutions, it’s worth the time to really evaluate the individual data points that can be collected through a decentralized process. Your team needs to go into the meeting confidently. The FDA will seldom object if you’ve thought through your execution strategy and have a solid rationale for your choices. Often, the biggest obstacle is the one we have placed on ourselves with our own limiting mindset.
How to Handle Change Management with Your Executive Team
The biggest challenge with adoption of decentralized trials is the risk aversion you may find across both your organization and with your vendors. If you have broad support from the C-suite level in your organization before you start to redesign your trial, you’re already ahead. But if you are proposing any changes and still need buy-in, support your value proposition with a data-driven approach. You will need to start at the top with your plan because if it’s been agreed upon at the top, then your clinical development team will have less reason to feel uncertain or wary of these significant changes.
Recognize that your executives’ biggest concerns are going to center around the current drug development timelines and corporate expectations for filings; executives typically build their timelines off durations of historical precedent with your programs. Your efforts to decentralize trials will save time on the back end, but you will need to build in time on the front end for the planning needed to get a pilot established. Always remember this is not an all-or-nothing approach; you can bring decentralized elements into your study design to de-risk approval from your management if you are struggling to obtain full support. If you define the elements of a decentralized approach that would fit into an NDA filing, it will likely appeal to executives’ risk aversion, and you may be able to start implementing small changes once you’re aligned.
Don’t underestimate the need for a robust change management process that accompanies the proposal for changes to your operating model, and for a review of your SOPs to ensure you are remaining compliant or modifying them to account for the new approach. Be sure to set milestones, goals, and create a written plan to show the organization where there are improvements in your approach for patients – show them how it and why it matters. Make it an actual internal improvement project and expect to devote your energy to articulating a compelling value proposition. Engage experts to help you if you don’t know where to start – they’ve likely been down this road a few times.
The Importance of a Technical Readiness Assessment
You will also need to conduct a technical readiness assessment before launching a decentralized trial. Your organization will need to have a plan, clear expectations, and educational components in place to enhance employees’ skills. In addition, you’ll need a dedicated team ready to support and integrate decentralized components into your portfolio. Without this, there will be organization pushback, inefficiency, and clunky integration. The best way to approach this is to conduct a gap analysis to look at trial design and trial execution to identify the modifications to accommodate this model.
The approach is not as simple as it sounds on paper. In addition, there is the need to collaborate with your vendors, sites, and patients. Perhaps the topic for part two – moving forward.
Join me on Wednesday, June 16, from 3:00 – 4:00 pm ET for the first live discussion in the “To the [end]Point” series, hosted by Peter Benton, to debate strategies for moving clinical research forward using COVID’s best lessons.