Management of clinical trials with new medications for cocaine dependence and abuse.

Clinical trials require a quite distinct shift in attitudes and procedures from ordinary clinical practice insofar as they require a proactive approach to patient recruitment, enrollment, and followthrough as well as significant attention paid to issues of documentation, regulatory compliance, and error prevention. Take documentation, for example: Today's requirement to have an independent record of clinical events that are recorded on the case report forms was until 5 or 7 years ago not addressed in as much detail as it is today. This is one of the first adjustments that the new investigator must address. The researcher must keep looking to see what is missing from the location and procedures as a study takes place in order to create the necessary patient base for doing the study and ensuring that all needs necessary to produce the result are in place and that procedures are done with as few errors as possible. Everything must be done in conformance with good clinical practice and the standards set by the protocol. The researcher must be willing to deal with a world of breakdowns such as missing data, and the failure of the patient to revisit the office within the appropriate time dictated by the protocol and within the window of time or grace period allowed by the study. The researcher must ensure that the patients comply with the dosing schedule and that they are trained to return medications for accurate pill counts. And so on. This means creating new procedures that are motivated by a commitment to producing a specific enrollment result defined by specific criteria and increasingly because of the press of time enrolled in a specific time period and put through a well-defined protocol process. Clinical research is dependent on a willingness to commit to a specific end result and do all that is necessary on a day-by-day basis to produce that result in terms of specific numbers, clean and accurate case report forms that are backed up by corroborating source documents in line with a specific timeline in which to accomplish the task, and an outreach effort to recruit and enlist patients, which may involve advertising and promotion of the program, all of which may contrast significantly with customary practice. Clinical research involves reliance on additional dedicated personnel who are critical parts of the research team, including the telephone screening person who must be trained to follow a script and at the same time to be aware of the nuances of enrolling appropriate and compliant patients. The entire staff must be made part of the process and must work in concert to recruit and maintain the patient in a study while being aware of the effect these efforts may have on the placebo effect. It also requires considerable training, review, and constant communication among the staff to ensure that the complex coordination of numerous patients and procedures works smoothly. There needs to be a willingness among the staff and the investigators to take correction from monitors who visit the site periodically and whose focus is on the quality of the data and not so much on the qualifications of the staff. This is not an action that people in nonresearch environments are trained to take. Failure to appreciate the complexity of conducting clinical trials can contribute to much frustration to everyone involved. When there is understanding of all the variables that influence the ultimate results, there is a willingness to anticipate breakdowns and to turn breakdowns into opportunities to create new structures and develop new procedures that will ultimately facilitate a successful outcome.