Clinical trials are inherently very complex, even for a simple trial, and yet at a high level they are relatively common and straightforward. There are small and large professional CROs who can handle the entire process, if provided with a protocol and drug supply. There are consultants and CROs who focus on some specific detailed aspect of the trial planning and execution process. The sponsor can organize a group of aspect-focused experts and thereby cover all needed trial functions.
Whatever path the sponsor chooses, they are responsible for satisfactory completion in order to get approval.
Under the Hood
Modern technology provides tremendous power and efficiency, but with a tradeoff in complexity and detail. Whereas early auto owners could fix almost anything in a car with simple tools, cars since about 1980 have become increasingly complex, with subcomponents increasingly computerized and interconnected. At the heart, a gas engine still has pistons, fuel/air, and ignition to cause the mixture to expand and move the piston. The details around that have great complexity to manage providing the right amount of fuel at the right time, and channeling the power from the moving piston.
Clinical trials “from 30,000 feet” need a trial design, regulatory blessing, drug supply, sites and trial operations, and a medical writing team. Looking more closely you need medical experts, patient interface, data collection and validation. Looking even more closely you need someone to greet the patient at each site visit, and make sure each patient has each needed dose. There are thousands of critical details.
As just one example, electronic data capture (EDC) provides a powerful tool for populating data in a clinical report form (CRF), the core of data management in a trial. There are providers who make only EDC tools. For any such tool, a sponsor can find multiple experts. Many CROs have experience with multiple EDC tools and are happy to discuss the strengths and weaknesses of various tools. A CRO may prefer one or two tools that integrate well with the rest of the CRO’s data systems, or CRO staff experience. Similarly, each EDC vendor, even small ones, has experience with many CROs, and can recommend a shortlist of CROs who work well with the EDC tool.
As another category example, some physicians have expertise with certain indications and are happy to host a site. Some of these are “first timers,” or have been involved in trials only a few times or perhaps infrequently. Getting them up to speed on your trial protocols may take more attention than if you use a higher volume trial site. However, at an experienced site conducting multiple trials, your trial may not get the attention you think it deserves.
Protocol adherence is important at any site whether using modern techniques, such as perhaps a new version of an EDC tool, or even older techniques. The question is how well does the site utilize the tool, and how well does the tool work in comparison to typical operations at a site. Remember, a busy site may well be using several different tools for various trials even simultaneously.
A trial of any size requires months of planning, and close supervision throughout, through first patient in, to last patient out, to final reporting, and regulatory submissions. Larger and international trials add complexity, often a great deal of complexity, and require appropriate scale in management attention.
Make or Buy?
It is critical to a successful trial to have a single individual who is in a position to decide how this trial will be or has been run well. That individual can integrate the input of a team, but ultimately one person needs to sign off on this.
A person signing off on any aspect of design, execution or completion needs to have viable perspective – basically years of experience with successful trials. That said each person has a first time doing any given task, so there will be people on the team who have varying degrees of experience. Some responsible person needs to understand and match skills with requirements with appropriate and sufficient management. This is for instance just one reason trials involve a fair degree of cross checking – site audits, entry error checking, validation – all of the various controls of a modern trial. And this checking function needs to be understood and managed properly.
This senior expertise often resides in the sponsor company, as a VP, or higher. In a large organization, managers may have the requisite experience to sign off on a major international trial. It is the person, not the title, which is important.
That said tiny virtual companies can conduct satisfactory trials. Typically, they would hire the requisite expertise through a consultant or CRO.
As a rough guide, the smaller the sponsor, the more experienced (and often larger) the CRO they need to engage. There are so very many parameters that impact this. Ultimately at least dozens of individuals will spend some time in properly conducting even the smallest of trials. Large trials require thousands of people, plus the subjects.
It is a rule of human nature that large groups make decisions more slowly. There are individuals and smaller teams that can make good decisions more quickly. Smaller groups have made plenty of poor decisions. Ultimately, there are groups that are more effective than others, and this is not dependent on the size or sometimes even the experience of the group. Companies that have grown to significant prominence have good management – period.
There is no substitute for having a good manager high in the approval stack for your trial. Good managers will be sure to hire good managers for sub parts of any process.
When I was a young professional working for a fancy New York City firm, one of the very top in the world, with rates to match, I wondered how the firm could charge such prices. The answer was actually fairly simple: we were the best, and our clients got the right result the first time in a very efficient process. The client could easily spend more for a less satisfactory and slower result from lesser firms. This is not to say that the biggest firms are necessarily the best. However, the firms with the best reputations usually deserve them, and they work hard to maintain a high level of service and keep their reputations polished.
Returning to our trial scenario, your trial will be most satisfactory if you have enough experienced, good managers in key positions. If these are external people, you need internal people to manage the outsiders.
Given the complexity of clinical trials, and the criticality to career and company success, it is essential to have an excellent manager very high in the supervision of any trial. That can be an internal or external person, but ultimately the sponsor needs to know that key person is capable and is responsibly watching the trial process.