Back to the future of clinical trials after COVID-19
The first 5 days in April 2020 22,229 people died from COVID-19.
After completing R&D and pre-clinical work, vaccine developers will start clinical trials in summer and early fall.
The biotech companies developing COVID-19 vaccines will then spend another cleaning 3–6 months cleaning data before submitting to FDA/EMA.
Translate 90–180 days into lives.
Back to the future
It’s a Monday morning in early June 1992 in Jerusalem. I’m a programmer-analyst looking after business data processing at the Intel Israel site. Chris Marshall — the site controller, pulls me into his cubicle and tells me about a revolutionary idea he has. Chris is calling it ‘continuous close’.
To understand the brilliance of Chris’s idea, you have to first understand the importance of timely reporting of results to the markets for a public company. Suppose your year-end is Dec 31. The company has revenue and profitability forecasts. Shareholders and the market want to know how you did. The SEC wants to know how you did. This is the function of the 10-K report.
The 10-K report is submitted to the SEC in a generic format, with no pictures or charts. The SEC has very strict guidelines on what information must be included and how it must be organized. It’s not designed for easy consumption for investors. 10-Ks tend to be very lengthy and more difficult to digest than annual reports. The good news is the rigid structure.
Let’s say you send your 10-K to the SEC sometime in June. Not good. End of Q1 also not good. People will be wondering if bad news is being withheld from the stockholders. The stock plummets. Confidence goes down the drain.
Now imagine that by Jan 7 — you’ve already closed the books and a computer program produces the 10-K and emails it to the SEC.
You’re a rock star.
Chris says, let’s not wait until the year-end. How about if every month we close the books and produce a 10-Q (the quarterly version of the 10K) for the month and a 10-K for year-to-date. Then on Dec 31 — we’ll press a button and and produce our 10-K for the whole year. Allow a week to get executive signature approval and you’re good to go.
And so it was my whole team (me and 2 programmers) spent the next 4 months writing and testing code. No one said it was impossible, so we did it. The test in October failed so we tried again in November and it worked. December that year, Chris pushed the button.
This was almost 30 years ago.
Today — clinical trials recruit patients, collect data and at the end of the experimental protocol, lock the data and then spend another 3–9 months cleaning data. While the CRO is cleaning data and churning billable hours, people are dying.
In an age of same-day delivery something does not compute.
Why Corona will accelerate the modernization of clinical trials
COVID-19 is disrupting our lives and the process of bringing new vaccines and therapeutics to markets via clinical trials.
It’s hard to quantify the cost to society of delays to COVID-19 trials, but consider that biotech and pharma companies are currently running more than 120 Phase 3 clinical trials with top-line data readouts expected before the end of the year. Without interpretable data from pivotal clinical trials, new vaccine and therapeutic filings will be delayed.
But it’s much worse than COVID-19. The COVID-19 pandemic has forced hundreds of clinical trials to grind to a halt, stalling research into cancer, strokes, dementia and more.
Even before the pandemic, life science companies were deeply concerned by the general reliability of data collected. A series of FDA guidance documents signaled that even a government regulatory agency wants the industry to do a use modern cloud technology like real-time data streaming and automated detection and response.
Beginning to sound familiar? Remember continuous close 30 years ago?
Clinical trials constitute an integral part of the drug development lifecycle and they rely on accurate and sufficient data for the validation of the study, and ultimately for its approval.
A series of 3–4 clinical trials can take 5–7 years. COVID-19 will accelerate that process but life science developers need high quality, interpretable data. Real-time data collection and automated detection and response is standard in every other transaction processing system we use today. Whether logistics (order shipment of a package and get a quote online in 60s) or online securities trading — we live in a real-time world.
Clinical trials recruit in range of 100s to 1000s of patients, all of whom need to comply to a clinical protocol. The data is often written down and paper and recorded in a Web application 3–5 days after the patient visit. So-called eSource apps eliminate the paper transcription step but leave a site monitoring visit or central monitoring function to look at the data and detect protocol violations. Protocol deviations are logged 5–7 weeks after the patient visited the clinic.
Rip out a paper-based process to achieve interpretable data online
The systems used by pharmas today were designed for paper-based process where it was acceptable to postpone data preparation to the end of the study. In the COVID-19 era, we don’t have that luxury anymore.
From recruitment to data collection to protocol adherence, the process creates enormous logistic challenges that need to be addressed by changing the fundamental assumption of paper-based, batch-based data processing.
With the current pandemic and the expected downstream effect, it seems obvious that this will have a massively adverse affect on patient participation and will be a major trigger in finding an alternative that empowers patients to complete the trials remotely and digitally.
Be ready every day to ship a vaccine
Yes, we need mobile data collection and great user experience for everyone participating in the clinical process — for patients, doctors and study nurses. Yes, we need to enable patients to participate from home when possible,
But we also need to be ready every day with the results by reengineering the process to use continuous close. Just like Chris Marshall did, 30 years ago at Intel.
It’s not a 10-K for the NASDAQ.
Its our lives and the lives of our loved ones.