Best Practices Spotlight

Be a nitpicker when it comes to IC form details

Check all signatures & dates

Thirty seconds is all it might take to prevent a weeks-long regulatory hassle.

That's what Eunice Newbert, MPH, tells clinical trial staff at Children's Hospital Boston (MA), where she is the manager of education and the quality improvement program.

Study coordinators should spend 30 seconds reviewing each signed informed consent (IC) form to make certain research participants signed these on the designated lines and dated these correctly, she says.

"If someone is asked to sign an informed consent form, they might sign the wrong line if they're given an option," Newbert says. "Parents might sign a witness signature line, and then the form is invalid, and you can't use that patient's data."

Researchers can correct these mistakes after the fact by reporting a deviation and then fixing them, but that takes much longer than a quick little review that is done before the subject leaves the room, she notes.

When research involves children or others who are unable to provide informed consent and need a guardian or other representative to sign the form, additional issues can arise.

Newbert offers these best practice tips for the IC process:

• Organize the IC template to reflect what the regulations require: Research sites could prevent common informed consent form mistakes through better organization of their informed consent template.

"Tailor the form for your study and to facilitate your consent process," Newbert suggests.

"This could be by changing the order of the signature line," she adds. "A lot of times principal investigators will sign the form before the subject, and that never makes any sense because the principal investigator (PI) or an organized consenter has to attest that the consent process happened correctly."

When the IC template has the PI's signature first, then people doing consent will obtain signatures in that order, so it makes sense to make the template reflect the process steps timeline, she says.

• Train staff to avoid fixing subjects' missing date lines: Another common mistake is for clinical trial staff to date a subject's signature when they discover this was left blank, Newbert says.

Again, that 30-second review could have prevented this problem. But if researchers discover blank date lines after the subject has left the building, then correcting the problem by adding in the date themselves could land them in regulatory hot water.

"I have read FDA warning letters, and next to the problems of enrolling ineligible subjects, the FDA has suspicions of researchers dating another person's signature," Newbert says. "The signature date is one of the few ways the FDA has to determine if the study began prior to the informed consent process."

Although study coordinators might believe it's a trivial difference — their putting in the date right after the subject signs the form, it is no small thing to regulators.

"It's supposed to be the subject attesting to the fact that they are signing the consent form on this date, prior to the first study procedure," Newbert explains. "If you are dating it, how do regulators know that the subject signed it prior to the first study procedure?"

The same reasoning applies if the subject has written in the wrong date.

"It's better to write a follow-up memo, saying, 'It was noted that the subject misdated it, however they attested to signing it on this [correct] date,'" she says. "Just don't correct it for them."

• Create an IC checklist: When clinical trials sites begin a quality improvement process to increase regulatory compliance they might create an informed consent checklist, Newbert suggests.

This should list every activity that needs to be done, including signatures, dates, parental permission, and assent, she says.

"Make it as specific as you like," Newbert says.

The checklist also should direct research staff to make routine back-up documentation of the IC process.

"If you lose a case report form you should be able to go back into your files, look at the medical records and verify that data," Newbert explains. "But if you lost the original consent form how would you know the consent process happened?"

• Require back up IC documentation: Invariably, there are studies with a missing consent form, so research sites need to prepare for that eventuality.

If a study coordinator loses a consent form, then he or she should have some other way of verifying the informed consent process took place, Newbert says.

"Go back into the medical records or clinical notes and say, 'At this date the informed consent was obtained,'" she suggests.

Then if a consent form is lost, the researcher should report it to the IRB, sponsor, and applicable agencies as a deviation. The study site might also obtain reconsent from the subject, but these actions are in addition to having the original consent process documented in other records or notes, she adds.

• Know when to reconsent subjects: If there is a change significant enough to influence subjects' decision to participate, subjects should be reconsented, Newbert says.

This change could involve adding study visits to the schedule or discontinuing a procedure that might have resulted in a personal benefit to the subject, she notes.

"Give subjects the choice of whether they want to continue," she adds.

• Always use the most up-to-date consent form: Even if an informed consent document was not changed, but an updated approval occurred during the continuing review process, study staff should use the form that has the latest IRB approval, Newbert says.

"This is one of the most common mistakes I would see," she says.

If a study coordinators has a new subject sign the earlier version of the IC form, then it's a deviation.

One way to prevent the use of dated forms is to build safeguards into electronic links to downloadable IC forms.

"What our institution did was create an informed consent library for the purpose of minimizing the use of nonactive consent forms," Newbert says.

"Researchers log into this IC library and download only the most recently approved version," she explains. "The link is available only on the IRB website, and we ask people to print out one or two copies."

The library will not permit the download of previous versions of the IC form, which solves one problem but raises two other issues, she notes.

One is that sometimes investigators lose their previous copies, which need to be kept on file, and they return to the library, thinking they can find the older version there. But the library cannot be used for that purpose. Researchers need to keep their own files of older versions of the IC form, Newbert says.

Secondly, on rare occasions, the IRB makes a mistake and has an incorrect version listed as the latest IC document, Newbert says.

"I tell PIs they're responsible for making sure that whatever they're downloading is current," Newbert says. "I tell them to not blindly use the form on the website because they still have to check it."