Almost ten years ago, I ran across a very disturbing statistic: 90% of all clinical trials experience significant delay! At first, I deemed it the exaggerated wailing of a disgruntled researcher. However, as I spoke with research directors and project managers across our industry, I came to understand that it was unfortunately true. But why?
The development of new veterinary therapies is complicated science, to be sure. But the conduct of clinical trials is a process, and all processes are controllable. All it takes is a dedicated project team, thorough planning, and meticulous execution. Assembling those three components, though, sometimes can be a challenge.
A dedicated project team is actually not quite what is needed. Today, everyone is “dedicated.” To run a successful clinical trial, everyone on the team must be focused…focused on complete and accurate data, focused on the timeline…in short, focused on the results that will make the trial a success.
A definition of the desired results is the first step in effective planning. I call it “reverse planning” because it starts with the end result and works backward, step by step, to the start of the trial. At each step, the question that the team must answer is “To achieve this desired outcome, what must happen first, and who is responsible for that?” Answering all of those questions as the team works back from the end of the trial to the start ensures that everyone knows what to do and nothing falls through the cracks.
With a focused team and a comprehensive plan, you are ready to execute! This is the heart of the clinical trial process. And, just as a human heart beats constantly, consistently, to sustain the body, the team’s attention to the daily activities of the various study sites must be constant and consistent. However, even experienced, hard-working, and well-intentioned team members have off days and make mistakes. I have found that the best way to minimize both the number and impact of those mistakes is to employ a series of detailed checklists for each activity. Checklists are especially valuable when time is short, and everyone is rushing to get things done.
Over the coming year, I will write ten articles, each dealing with an important step in the clinical trial process, and all aimed at cutting that 90% statistic down to a more tolerable level. I call this series my Ten Tips for Tremendous Trials.
My ten tips are:
- Clear expectations
- Comprehensive planning
- Effective investigators
- Rigorous training
- Proactive subject recruitment
- Timely data review
- Diligent monitoring
- Investigational Veterinary Product (IVP) controls
- Frequent communications
- Careful close-out
Setting Clear Expectations
Let’s start with my first tip. One of the most effective ways to prevent problems during a clinical trial is to convene a meeting of all project team members before the study even begins. Without the time pressures that inevitably surface once sites have been initiated and study subjects are being enrolled, everyone can voice their expectations and explain what they perceive their role to be. Be prepared for some interesting revelations!
These discussions should be very specific and detailed. I recommend role-playing through lots of “what if” scenarios. I also recommend that two or three extra chairs be included in the room, one for a study investigator, another for a subject owner, and a third for the CRO if one is being used to manage the trial. During role-playing, someone should sit in those chairs to provide some of that external perspective.
For example, a sponsor or CRO would expect an investigator to:
- actively participate during training;
- set aside an appropriate amount of time to perform their study obligations;
- make a concerted effort to recruit eligible subjects;
- follow the protocol exactly;
- enter data in a manner that is complete, legible, and correctly formatted;
- answer queries in a timely manner; and
- report adverse events and protocol deviations promptly.
An investigator would expect the sponsor or CRO to:
- provide clear and complete training;
- provide technical and logistical support;
- deliver adequate IVP and related supplies;
- promptly respond to questions;
- review data forms quickly;
- pay on time for completed work; and
- provide compassionate care and/or rescue treatment for adverse events.
A subject owner would expect the investigator to:
- provide complete, clear, and honest explanations of the study;
- provide clear, easy-to-follow instructions for owner responsibilities;
- provide adequate supplies of IVP and related materials;
- promptly answer questions;
- provide compensation for inconvenience and/or performance; and
- provide treatment for adverse reactions to the IVP.
A sponsor would expect a CRO to:
- ensure that all investigators follow the protocol exactly;
- ensure that only eligible subjects are enrolled;
- deliver complete and accurate data;
- ensure that exact IVP inventory control is maintained;
- provide regular study progress reports;
- ensure that any adverse events or other problems are promptly reported; and
- adhere to the study budget and timeline.
A CRO would expect a sponsor to:
- provide a synopsis or a complete protocol, including all data forms;
- actively participate in investigator training;
- attend regular project team meetings or teleconferences;
- promptly answer questions;
- pay on time for completed work and expense reimbursements; and
- approve and provide compensation to investigators for rescue treatment for adverse events.
Your study planning meetings undoubtedly will add many other responsibilities to the above lists. The important point is that you convene these meetings and require all project team members to attend and actively participate. Anticipating potential problems, and developing strategies and solutions, in advance of their occurrence, is vastly preferable to scrambling to pick up the pieces during the stress of a study. It also prevents the kind of mistakes that often lead to disqualified data and needless study delays.
I would be very interested in your thoughts about each of these ten articles. So, if you agree with, disagree with, or want to comment on anything in my articles, please email me at email@example.com. Together, we can improve the effectiveness of clinical trials and enhance the quality of the data they produce. What a great goal for the new year!