Complicated Disclosure Rules
Researchers released a report analyzing the complicated state of affairs surrounding publication of medical and scientific literature about cancer research. The report’s findings include data about the amount of information required to be disclosed by researchers as well as the type of information disclosed.
One startling statistic in the report shows that a significant number of journals (19 out of 131) have no disclosure requirements of researchers. Many believe that research funded by companies with an interest in the results should be viewed with skepticism and research into bias in medical literature lends credence to this theory.
The legal profession provides an interesting contrast because ethics rules require checking for conflicts of interest before representing a client. Even if only a potential conflict of interest, almost all conflicts are disclosed to the client or representation is declined. These rules are enforced by state bar associations who also hold power over lawyers’ licenses to practice. Because there is no such authority over the field of scientific research, the rules vary from publication to publication. For instance, the term ‘conflict of interest’ had various meanings, depending on the journal.
While the general public might view this as a very remote problem, companies are keenly aware that such literature is sometimes the only source of information upon which doctors make prescribing decisions besides labeling information. Thus, positive treatment in an article where certain drawbacks should also be brought up often has measurable effects on which treatments patients receive.
Queries in Clinical Trials
There are many important components to study and analysis of adverse events in clinical trials. The term “Queries” in this context is typically used to refer to questions which the sponsor poses to the clinical investigator regarding details of adverse events.
“Queries” are meant to represent both a critical quality assurance mechanism, but they are actually a weak point in many clinical trials. Some of the issues regarding proper implementation of queries are discussed today.
Typically the Case Report Form for a clinical trial will have a separate page on which adverse events occurring during visits or between scheduled visits should be recorded. There are several classes of information which this form attempts to gather:
- The date and time of the event
- Description of the adverse event.
- List of all of the medications the patient was on at the time of the adverse event and in the days preceding it.
- Treatments administered.
- The course of the patient.
- The investigator’s classification of the event (as to whether it is serious, unexpected according to the investigator booklet, and whether it is related or unrelated to the drug being tested).
Unfortunately, it is not uncommon for a busy nurse or clinical trial assistant, in the course of treating the patient suffering from an adverse event, to neglect to fill in some of the data points on the form. Some interestigator sites do not have a mechanism of routinely ensuring review of the adverse event form by a second person before the form is submitted to the sponsor. It is the responsibility of the sponsor to ensure that all the appropriate data is gathered. This includes not only the standard demographic and clinical trial detail information. but also the narrative sequence of treatments administered and the time course of the patients illness and recovery.
Some progress in improving the process of recording and documenting adverse events has been seen with the introduction of Electronic Data Capture. These electronic systems have what are called Automatic Edit Checks so that clerks, doctors or nurses entering data into the computer must complete all of the fields, and enter the data in a defined format, or they cannot complete the form. However most clinical trials in the United States and worldwide are overwhelmingly still done on paper. The problem of illegible notes, incomplete notes, implausible narratives, or in the worst case, notes which are entered later but are not documented to have been entered later, information about important adverse events can be lacking or confusing.
In subsequent blogs, we will review some of the steps that both clinical investigator sites and sponsors can take to help ensure the quality and thoroughness and timeliness of the query process.