To fix trials, we need to pay attention to the boring stuff
Trial operations are getting less productive and more expensive. That needs to change.
This post is part of the Clinical Trials Efficiency Project. The purpose of the project is to identify and promote reforms to make trials faster and cheaper. If you have ideas on how to make clinical trials more efficient, please email me.
There is a vast gulf between how the pharmaceutical industry sees itself and how the public sees it. To the public, the pharmaceutical industry is venal and corrupt, putting profits above patients’ needs. But when I speak to those who work in the industry, they are deeply mission-driven: many enter the field with sincere hopes of discovering treatments and cures for the world’s most devastating diseases.
At the heart of this mission are the scientists who discover new drugs. They’re the reason the industry exists, and they represent how pharma wants to be seen. If you visit a drug company’s website, you’ll find stock photos of them: They’re the intrepid researchers, toiling away in their lab coats, on the cusp of their next breakthrough. If the industry has a ladder of prestige, these scientists sit at the top of it.
Also near the top of the prestige hierarchy are those who work on clinical trial design. They may not discover new drugs, but they make decisions that can make or break a drug development program. Their work requires deep scientific expertise, regulatory knowledge, and creativity.
Many rungs below sit the people who actually test the drugs and prove they work. These are the “boring things after the creative, exciting part is done,” including the mundane but necessary work of “clinical operations”: setting up trials, negotiating payments, recruiting patients, collecting data. Even among those who work in the field, this is often considered the “unsexy”, “boring” part of drug development.
The field of clinical operations lacks drama and gets little attention. The industry, its leaders, and its investors focus on big milestones: a “go / no-go decision”, a high-stakes FDA meeting, the start of a $100+ million dollar trial, the pivotal readout that determines a program’s fate. By contrast, trial operations are a day-to-day grind. There are few big moments to celebrate. I suspect many CEOs spend relatively little time thinking about it.
But we desperately need to improve trial operations if we want to make clinical trials more efficient.
Trial operations have gotten less productive
That’s because trial operations are what drives trial costs, and those costs are rising fast.
To understand the rise in costs, it’s useful to understand how drug industry trials are typically run. Drug companies pay for trials, but they aren’t the ones who carry them out. Rather, their main job is to develop the trial protocol, which lays out how the trial ought to be run: who is eligible participate in the trial, what procedures should be run, what data should be collected, and how that data should be assessed. The work of running the trial itself is usually outsourced: Contract research organizations (CROs) coordinate and oversee the trials, and research sites—including large academic medical centers and research clinics—carry out the protocol.
As research sites do the bulk of the hands-on work of running the trial, they also incur the largest portion of the trial’s cost. Site costs have risen rapidly in recent decades. One analysis showed that site costs for phase 3 trials rose from $11,630 per patient in 2000 to $23,711 in 2011—an increase of nearly 10% per year. While we lack more recent data on site costs, other data suggests they are continuing to rise: a more recent study which measured total trial costs (not just site costs) found that phase 3 trial costs had reached $55,567 per patient by 2017. Meanwhile, as costs have risen, trials have also gotten slower. They take longer to set up, longer to enroll patients, and longer to complete. Those costs and delays limit how many drugs ultimately make their way to patients.
One reason that trial costs are rising is that the trials have grown more complex. Drug companies are collecting more data, running trials across more sites, and measuring more endpoints. They are also placing tighter restrictions on who can enroll. Some of the increases in complexity are scientifically justified, but much of it looks like bloat. This complexity drives up costs and puts strain on the trial sites. Trials are being optimized for regulators and risk-averse managers—not for the sites that actually have to run them.
But complexity isn’t the whole story. If we take a closer look at site costs, we find that they have risen even after accounting for the increased complexity, and faster than inflation in the health and research sectors. In other words, the trials industry, which already lagged in its use of technology by the turn of the century, has probably gotten less productive over time.
This won’t surprise people who work in clinical operations. While drug companies and trial sites take great care to adhere to protocols, procedures, and regulations, there is very little about the process that is automated or streamlined. Brandon Li, a clinical trials entrepreneur, remarked that “clinical trials are $200m group projects held together by duct tape and project managers.” If you’ve ever worked for an over-stretched and understaffed organization, you can picture the failures: manual transcription across paper and computer systems, reliance on ad-hoc spreadsheets, lost logins and passwords, inboxes full of missed emails, stalled contract negotiations, and unpaid invoices. Somehow the work gets done, but it feels much harder and less efficient than it should.
If that picture sounds discouraging, I’d like to emphasize the good news here: these problems are fixable. Making trials dramatically more efficient doesn’t require us to invent new science or technology. It doesn’t require us to reform the FDA. We don’t even need AI. (All of these things would be helpful, though!) All we really need to do is fix the basic stuff: stop using paper, stop transcribing information manually between systems, stop wasting time on useless administrative tasks, and stop making the protocols so needlessly complex. In other words, we just need to do the kinds of operational modernization that other industries have been doing for ages.
Fixing trials is boring, hard work
If the fixes are so basic, why haven’t we done them already? I suspect it’s because the work is too boring–and not prestigious. In an industry that prizes scientific creativity and expertise, operations don’t get much attention. Fixing trial operations and designing trials that are easier to run requires sustained focus and coordination. It won’t make big headlines in the trade press.
A lack of attention makes reform harder. Consider the problem of risk aversion. I have interviewed industry experts and insiders - and nearly all of them mentioned that operations are run in a deeply risk-averse way. Managers at drug companies would rather stick to tried-and-true approaches to running trials than try to reform them and risk regulatory scrutiny. This risk aversion has downstream effects on the entire trials industry. Since drug companies are reluctant to embrace innovative cost-cutting measures, CROs face little incentive to cut costs. And without sponsor support, it’s hard for trial sites to improve their operations.
But behind many cases of risk aversion lies a deeper problem: a lack of leadership attention. Risk aversion isn’t unique to pharma. You will struggle to find a middle manager in any large organization who is willing to be bold unless they have visible backing from leadership. As long as industry leaders neglect clinical operations, managers will default to doing what they’ve always done and productivity will stagnate.
And trial operations need a lot of attention. It’s difficult to change such a fragmented, entrenched, and heavily regulated system. Anyone in the industry seeking to make even a small improvement in trial operations must navigate a tangled web of contracts, regulations, and SOPs. Each of their business partners—whether they are sites, sponsors, or CROs—will handle things differently. There are also larger-scale coordination problems: sponsors can’t run more efficient trials unless the sites agree to modernize their operations. Sites can’t modernize their operations unless all of their sponsors agree on what that modernization should look like.
That means that there are no quick fixes. We don’t lack the knowhow or technology to improve how trials run; we lack the ability to deploy improvements at scale. We can’t just send consultants in to make trials more efficient, and there’s no B2B SaaS tool that will transform the industry. Improving the efficiency of trial operations will take hard work and focused attention. Policymakers and the government will probably have to get involved too.
If we want to make trials more efficient, we need to pay more attention to the boring stuff. We need to measure it and prioritize it. That’s part of why I created the Clinical Trials Efficiency Project. When it comes to improving clinical trial efficiency, there’s a role for new trial designs, new science, new technology, and new ideas. But I also hope we can bring attention to the boring bottlenecks that make trials inefficient and have remained neglected for too long.
Adam
the pharmaceutical industry is venal and corrupt, putting profits above patients’ needs. But when I speak to those who work in the industry, they are deeply mission-driven: many enter the field with sincere hopes of discovering treatments and cures for the world’s most devastating diseases.
At the heart of this mission are the scientists who discover new drugs. They’re the reason the industry exists, and they represent how pharma wants to be seen. If you visit a drug company’s website, you’ll find stock photos of them: They’re the intrepid researchers, toiling away in their lab coats, on the cusp of their next breakthrough. If the industry has a ladder of prestige, these scientists sit at the top of it.
Also near the top of the prestige hierarchy are those who work on clinical trial design. They may not discover new drugs, but they make decisions that can make or break a drug development program. Their work requires deep scientific expertise, regulatory knowledge, and creativity.
Many rungs below sit the people who actually test the drugs and prove they work. These are the “boring things after the creative, exciting part is done,” including the mundane but necessary work of “clinical operations”: setting up trials, negotiating payments, recruiting patients, collecting data. Even among those who work in the field, this is often considered the “unsexy”, “boring” part of drug development.
The field of clinical operations lacks drama and gets little attention. The industry, its leaders, and its investors focus on big milestones: a “go / no-go decision”, a high-stakes FDA meeting, the start of a $100+ million dollar trial, the pivotal readout that determines a program’s fate. By contrast, trial operations are a day-to-day grind. There are few big moments to celebrate. I suspect many CEOs spend relatively little time thinking about it.
But we desperately need to improve trial operations if we want to make clinical trials more efficient.
Trial operations have gotten less productive
That’s because trial operations are what drives trial costs, and those costs are rising fast.
To understand the rise in costs, it’s useful to understand how drug industry trials are typically run. Drug companies pay for trials, but they aren’t the ones who carry them out. Rather, their main job is to develop the trial protocol, which lays out how the trial ought to be run: who is eligible participate in the trial, what procedures should be run, what data should be collected, and how that data should be assessed. The work of running the trial itself is usually outsourced: Contract research organizations (CROs) coordinate and oversee the trials, and research sites—including large academic medical centers and research clinics—carry out the protocol.
As research sites do the bulk of the hands-on work of running the trial, they also incur the largest portion of the trial’s cost. Site costs have risen rapidly in recent decades. One analysis showed that site costs for phase 3 trials rose from $11,630 per patient in 2000 to $23,711 in 2011—an increase of nearly 10% per year. While we lack more recent data on site costs, other data suggests they are continuing to rise: a more recent study which measured total trial costs (not just site costs) found that phase 3 trial costs had reached $55,567 per patient by 2017. Meanwhile, as costs have risen, trials have also gotten slower. They take longer to set up, longer to enroll patients, and longer to complete. Those costs and delays limit how many drugs ultimately make their way to patients.
One reason that trial costs are rising is that the trials have grown more complex. Drug companies are collecting more data, running trials across more sites, and measuring more endpoints. They are also placing tighter restrictions on who can enroll. Some of the increases in complexity are scientifically justified, but much of it looks like bloat. This complexity drives up costs and puts strain on the trial sites. Trials are being optimized for regulators and risk-averse managers—not for the sites that actually have to run them.
But complexity isn’t the whole story. If we take a closer look at site costs, we find that they have risen even after accounting for the increased complexity, and faster than inflation in the health and research sectors. In other words, the trials industry, which already lagged in its use of technology by the turn of the century, has probably gotten less productive over time.
This won’t surprise people who work in clinical operations. While drug companies and trial sites take great care to adhere to protocols, procedures, and regulations, there is very little about the process that is automated or streamlined. Brandon Li, a clinical trials entrepreneur, remarked that “clinical trials are $200m group projects held together by duct tape and project managers.” If you’ve ever worked for an over-stretched and understaffed organization, you can picture the failures: manual transcription across paper and computer systems, reliance on ad-hoc spreadsheets, lost logins and passwords, inboxes full of missed emails, stalled contract negotiations, and unpaid invoices. Somehow the work gets done, but it feels much harder and less efficient than it should.
If that picture sounds discouraging, I’d like to emphasize the good news here: these problems are fixable. Making trials dramatically more efficient doesn’t require us to invent new science or technology. It doesn’t require us to reform the FDA. We don’t even need AI. (All of these things would be helpful, though!) All we really need to do is fix the basic stuff: stop using paper, stop transcribing information manually between systems, stop wasting time on useless administrative tasks, and stop making the protocols so needlessly complex. In other words, we just need to do the kinds of operational modernization that other industries have been doing for ages.
Fixing trials is boring, hard work
If the fixes are so basic, why haven’t we done them already? I suspect it’s because the work is too boring–and not prestigious. In an industry that prizes scientific creativity and expertise, operations don’t get much attention. Fixing trial operations and designing trials that are easier to run requires sustained focus and coordination. It won’t make big headlines in the trade press.
A lack of attention makes reform harder. Consider the problem of risk aversion. I have interviewed industry experts and insiders - and nearly all of them mentioned that operations are run in a deeply risk-averse way. Managers at drug companies would rather stick to tried-and-true approaches to running trials than try to reform them and risk regulatory scrutiny. This risk aversion has downstream effects on the entire trials industry. Since drug companies are reluctant to embrace innovative cost-cutting measures, CROs face little incentive to cut costs. And without sponsor support, it’s hard for trial sites to improve their operations.
But behind many cases of risk aversion lies a deeper problem: a lack of leadership attention. Risk aversion isn’t unique to pharma. You will struggle to find a middle manager in any large organization who is willing to be bold unless they have visible backing from leadership. As long as industry leaders neglect clinical operations, managers will default to doing what they’ve always done and productivity will stagnate.
And trial operations need a lot of attention. It’s difficult to change such a fragmented, entrenched, and heavily regulated system. Anyone in the industry seeking to make even a small improvement in trial operations must navigate a tangled web of contracts, regulations, and SOPs. Each of their business partners—whether they are sites, sponsors, or CROs—will handle things differently. There are also larger-scale coordination problems: sponsors can’t run more efficient trials unless the sites agree to modernize their operations. Sites can’t modernize their operations unless all of their sponsors agree on what that modernization should look like.
That means that there are no quick fixes. We don’t lack the knowhow or technology to improve how trials run; we lack the ability to deploy improvements at scale. We can’t just send consultants in to make trials more efficient, and there’s no B2B SaaS tool that will transform the industry. Improving the efficiency of trial operations will take hard work and focused attention. Policymakers and the government will probably have to get involved too.
If we want to make trials more efficient, we need to pay more attention to the boring stuff. We need to measure it and prioritize it. That’s part of why I created the Clinical Trials Efficiency Project. When it comes to improving clinical trial efficiency, there’s a role for new trial designs, new science, new technology, and new ideas. But I also hope we can bring attention to the boring bottlenecks that make trials inefficient and have remained neglected for too long.
Adam