Eat your vegetables

Many people think of clinical research as a relatively modern development. However, scientific comparisons of competing theories have been conducted for centuries. For example, one of the earliest recorded trials was conducted in 530 BC.

“Then Daniel said to the steward…

Test your servants for ten days; let them be given vegetables to eat and water to drink. Then let their appearance and the appearance of the youths who eat the king’s rich food be observed by you, and according to what you see, deal with your servants.

So the steward harkened to his servants in this matter; and tested them for ten days.

At the end of ten days, it was seen that the steward’s servants were better in appearance and fatter in flesh than all the youths who ate the king’s rich food. So the steward took away the rich food and wine that his servants had been consuming, and gave them vegetables.”1

During the mid-1700s, scurvy was the scourge of the British fleet. In an attempt to cure this often-fatal disease, naval surgeon James Lind compared alternate therapies among three groups of sailors.2 This may have been the first floating clinical trial.

As more such tests were conducted around the world, scientific investigators began to exchange ideas and compare methods. Gradually, certain practices became more accepted than others. However, these practices were neither complete nor consistent, and not every investigator followed them.

That changed for the veterinary world in 1996, when the International Conference on Harmonization of Technical Requirements for Registration of Veterinary Products (VICH) was created to “establish and monitor harmonized regulatory requirements for veterinary medicinal products in the VICH regions (the US, EU, and Japan) to meet high quality, safety and efficacy standards and minimize the use of test animals and costs of product development.”3 VICH, together with Good Clinical Practice Guidelines (GCPs), drew together lessons learned by clinical trialists and regulators over many years to set a new comprehensive standard for clinical research.

So, today, how do we assure that every investigator is “following the rules” and producing reliable data? Diligent enforcement of industry regulations is one way. Comprehensive training prior to the start of each clinical trial is another.

Based on my experience in both human and veterinary trials, I believe that almost any capable and motivated veterinarian can be a successful investigator. The challenge is determining the best way to train them in the protocol, relevant regulations, and GCPs while defining “best” in terms of protocol amendments, protocol deviations, overlooked adverse events, data error, and/or other factors.

After a recent study training meeting, we surveyed attendees as to which training methods best prepared them for the upcoming trial.

Of the 60 participants at the training meeting, 74% had at least 10 years of clinical trials experience, 11% had participated in clinical trials for more than 10 years, and 15% had more than 20 years of experience. Of the 44 who completed our questionnaire, all had completed at least 6 trials and some had completed several more.

When asked about centralized versus on-site training, almost 80% preferred a centralized meeting because it allowed direct discussions with the sponsor about the protocol and study objectives. However, equal percentages (73%) felt comfortable performing their study responsibilities after completing either type of training.

Slightly over 70% attended training because they were compensated and about 15% were strongly influenced by the location of training. Just under 60% of the responders felt that an 8-hour centralized meeting was adequate while 25% indicated it was too short.

Regardless of venue or duration, the goal of training is a team of investigators who can enroll eligible study subjects quickly, follow the protocol, and provide complete and accurate data. Our goal as study managers is to determine the best way to accomplish this.

References

1 Daniel 1:11-16, c. 530 BC

2 Carlisle, Rodney (2004). Scientific American Inventions and Discoveries, p.393. John Wiley & Sons, Inc., New Jersey

3 VICH, 2005