Improve case report form documentation
Queries can be a hassle for everybody
The way case report forms are handled can slow or expedite a clinical trials process, which ultimately will impact efficiency, workflow, and costs.
"This is one of those areas where there are various ways of handling the data," says Peggy Pence, PhD, president and chief executive officer of Symbion Research International Inc. of Agoura Hills, CA. Symbion is a contract research organization (CRO) and consulting firm that provides full service in all aspects of clinical study design, conduct, and management.
"Some sites primarily use computerized edits on data, and others do thorough review of data by someone who is medically trained," she reports. "They review [them] to determine whether queries or clarifications are needed before the database is finalized."
Once the queries are answered, they have to be reviewed again and the database is updated, Pence adds. "Sometimes, the queries are a hassle for everybody involved. Every time you handle a piece of paper it requires time and energy, and so if you could reduce queries going back to the site then you could improve work flow and reduce time and cost."
She offers these suggestions for improving case report forms and reducing queries:
- Capture electronic data early. Electronic data could be reviewed prior to the scheduled monitor’s review and, if a site doesn’t have electronic data, then case report forms could be faxed to the study’s internal data management group that’s in charge of quality control prior to monitoring, Pence explains. "If data are submitted early, quality control staff could give a site feedback about any misunderstandings."
Although the monitor has not looked at the data and verified them, this strategy still might be useful for catching early mistakes that could become bad habits and trends, Pence notes.
The quality control people could advise a site that they misunderstand certain information, but won’t provide an official query answer until after the data monitoring takes place, she explains.
"We don’t want to create a conundrum of getting responses to incorrect data that the monitor then has to go back and revise," Pence says. "If the quality control staff do generate a query, they’ll send it to the monitor and site with instructions that the query should be addressed with the monitoring visit."
The type of mistake that could be caught early on includes one in which a clinical trials coordinator misunderstands how the case report form is worded or misunderstands the intent of the protocol, she says.
- Write a consistent and clear case report form. The case report form should accurately reflect the protocol and remain consistent in how it answers and asks questions, leaving no room for misinterpretation, Pence says.
"You certainly want to work very vigorously to achieve the straightforward case report form," she says. "But having said that, because of the complexity of clinical trial process and questions asked, it’s been my experience that no matter how well designed a case report form is there still will be some problems with misunderstandings."
For example, if a case report form asks for yes and no responses, using boxes to be checked, then all of the "yes" boxes should remain in one column and the "no" boxes in another, Pence says.
"People get used to seeing the yes’ box in the first column and then the no’ box in the second, so if you switch it on a second page, they’ll enter quickly without looking at the header, and you will get incorrect answers," she explains.
Case report forms also should have questions and statements worded in as clear a way as possible, so there is not room for ambiguity, Pence says.
- Go over the case report form with staff who will complete it. "Go through a case report form in detail with those who are responsible for completing it and encourage people to have an open communication and to call with questions if they’re unclear," she says. "There should be a contact person at the sponsor or CRO for a person to contact with questions."
Often sites will have the monitor be the point person for any questions, but this may limit a clinical trials coordinator’s ability to get quick answers since monitors often are traveling and unable to return calls promptly, Pence notes. "In our own organization, we have the sites contact the internal people who are working on review of the case report forms."
The CRO’s contact people understand the role of the people who contact them and are able to provide answers and clarifications immediately when called, Pence notes.
Also, sites should have manuals outlining how to use the case report form available to staff. These should provide examples of how the case report form should be completed and point out any areas that potentially could be misunderstood and clarify those, she says.
"That’s a ready resource at the beginning of a study, and at the beginning of the study, during site initiation, the monitor is responsible for going through the case report form in detail with all those involved in completing it," Pence says.
"Some studies have an investigator meeting at the outset, and often the study coordinators will be included at the investigator meeting," she says. "We recommend a breakout session for study coordinators."
Furthermore, at each monitoring session, the monitor should review the form and clarify any troublesome issues with staff.
- Start process improvement if mistakes become a trend. If sites are consistently misunderstanding how something needs to be completed or if there’s a trend of forgetting to complete some part of the case report form, then the case report form will need to be amended and/or the clinical trials staff re-educated, Pence says.
"But it’s much easier and it decreases problems if you can catch a mistake before the case report form is utilized for data collection," she notes. "And that’s done by a quality assurance audit before it’s distributed for use."
In cases where a potential snag wasn’t caught before the case report form is distributed, then it should be addressed as soon as it’s discovered, Pence says. "If questions are not answered, then you need to go back to the form and make sure the case report form and the way questions are asked is consistent with the protocol."
For example, if a protocol calls for both male and female subjects, then the question regarding whether the subject has had a pregnancy test should include a box for "not applicable," to avoid all misunderstanding, Pence says.
- Watch for common case report form mistakes. "Be sure the date formatting is correct," she says. "Use the same date formatting throughout the document, or if it’s going to be month, day, year, or better — for international studies — use letters for the month because Europeans reverse the order of the month and day of the month."
Then, however the date is written, it should be written the same way throughout the form, Pence adds. Also, abbreviations should be spelled out for the people completing case report forms so there will be no misunderstanding about what the abbreviations stand for, she says.
- Add a column for sponsor notes. "We like to see a column on the left-hand side of the case report form that we label for sponsor’s use only so that notes can be written within that column," Pence says.
These notes may include items given to data entry staff for clarification, which may improve the workflow since the data entry staff won’t have the same backgrounds as the people who are reviewing the data internally. "So if by virtue of their background and education there’s a medical term that’s difficult to read, the notes would explain it," she explains.
"You can do clarifications in that column for the next group handling the case report form, and you can add clarifications to reduce duplication and queries," Pence says.
- Ask questions for all of the data that will be analyzed. "It’s important to ask questions you intend to analyze and to not ask for information you won’t analyze," Pence says.
"This already is a tedious and expensive process, so be sure in the protocol and case report form that you’re asking all the necessary and appropriate questions, but not just collecting data for the sake of collecting it," she says.
On the other hand, it’s important to be proactive in anticipating information that will be important to a study, because if something is not collected in the case report form, the study may be less successful, Pence says. "The foundation for a good case report form is a very well-designed and well-written protocol."