The Trouble with Clinical Trials: Getting Rid of Zombies

Let me tell you a scary Halloween story…

It’s getting harder and more expensive to develop new medicines. Clinical development is taking 25% longer than a decade ago. The likelihood of a new medicinal product getting market approval has halved since then.

Most of the money and time spent in developing new drugs goes to clinical trials. Considering this, you might expect that clinical trials are constantly adapting to optimize speed, efficiency and safety. Well… unfortunately, no. I did my first clinical trial in 1984. I have to say that trials now look a lot like they did then, which is scary.

On the other hand, there is a 10% annual increase in the number and variety of procedures required. Thus, the burden on investigators and trial sites is steadily becoming heavier. In fact, I marvel at the level of complexity in some of the protocols I see. It is little wonder that we are seeing a high turnover of investigators. The so-called “one and done” investigator unfortunately isn’t a cliché.

Zombies Haunting Clinical Trials

The main zombie from the past that continues to haunt trials today takes the form of paper and paper-like PDF protocols. These are almost always thick, weighty documents of densely printed pages. They usually “live” on a shelf in an office, frequently remote from the clinical area where they are needed most.

When you get to the office where protocols are kept, then the fun begins as an investigator:

• You must first find the right protocol among stacks of binders, which is especially challenging for sites running multiple trials at any given time.

• You must make sure it’s the correct version, which is a constant worry considering there could be half a dozen amendments during the life of a trial.

• You then have to start sifting through pages to find your answer, which hopefully is clear enough to take a decision. If not, another nightmare of getting timely clarifications from the CRA or study team begins.

Even if the protocol is securely stored as a PDF somewhere in a portal, searching for answers is a nuisance. It starts with the hassle of logging into the correct portal. With dozens of them, remembering the right username and password is a fright.

It is no surprise that about 35% of adverse findings of FDA inspections are related to non-compliance with the protocol. This is not just bumps in the night!

Horror for Investigators

Zombie documents refuse to die. In a world where most of us acquire information instantly with our smartphones, paper and paper-like PDF protocols drag us back to the last century. While there may be aesthetic joy in holding a real book compared with an e-reader, this hardly applies to investigators with trial protocols.

As an investigator, I may run a dozen different trials at once. Will I realistically remember the detailed inclusion and exclusion criteria for each trial as I sit in my clinic seeing patients? My trials office is in a different building. Time constraints mean that I have only a few minutes to consider whether a specific patient might qualify for one of these trials. And there’s a restless line waiting outside. I’m highly unlikely to rummage through a dozen protocols to check. I might refer to a “cheat sheet” with the criteria listed. But is it up to date from the latest amendment? As you can imagine, I’m more likely to move along to the next patient, meaning another possible trial participant misses out.

The zombie strikes again!

I need to carefully look after my patients as an investigator. However, adverse effects don’t respect office hours. Consider the following scenario. It’s 8 p.m. on a Friday. I am about to sit down to a fancy anniversary dinner with my beloved. A study participant phones urgently to report sudden onset bloody diarrhea and is desperate to know what to do. My paper protocol is in a different city. How will I instruct the participant exactly according to the protocol? What if I just try to recall the protocol details and hope that I am correct? If I’m wrong, it may result in harm to the participant and the trial.

A zombie has just grabbed a leg!

Giving Trials the Best Chance to Live

To effectively deal with the many pitfalls of relying on printed and paper-like PDF protocols, we need to bring the whole process into the 21st century. To match the accessibility of information in every other aspect of our lives, we need to make protocols truly digital, searchable, mobile, and at the point of care - where they are urgently needed.

Today, I would resolve a bar dispute about who won the Super Bowl the year I was born by finding the answer on my smartphone. I wouldn't seek out the NFL printed yearbook. (It was the Cleveland Browns, if you are curious). I need the same option when assessing if my patient can join a trial or reviewing what to do about his bloody diarrhea – answers anytime, anywhere from my mobile device.

The zombie paper protocol is making it more difficult to be an effective investigator. There is no logical reason for its continuing existence. Let’s put it to rest and move on to breathe life into our trials.