QA program checks consent form accuracy

Organization maintains copy of every signed form

For more than 30 years, the National Surgical Adjuvant Breast and Bowel Project has collected copies of every consent form signed by the more than 130,000 patients enrolled in its clinical cooperative group trials.

But that wasn't what led to this year's best practice award in human subjects protection by the Health Improvement Institute. Rather, the NSABP received the award for what they do with the forms, checking them against the original template consent forms approved by the group in an effort to find and eliminate errors that make their way onto local forms.

"We just felt in the spirit of making sure that patients are consenting to a trial as we planned, we thought the best thing to do was to monitor the language," says Walter M. Cronin, MPH, associate director for operations at the NSABP Biostatistical Center in Pittsburgh, PA.

Cronin says that as his organization collected consent forms from participating institutions over the years, repeated analyses showed variations from the template forms that the NSABP had originally approved for the studies.

In many cases those variations, through "errors of commission or omission," inaccurately stated the risks and benefits of the studies they described (when these cases turned up, patients were reconsented). A review of consent forms conducted 10 years ago showed that 10% of forms had serious anomalies that could affect the subjects' understanding of the trials.

Some of these changes have been the result of local IRB reviews, when an IRB requires boilerplate language to meet local requirements. But Cronin says that isn't the only factor.

"One of the worst potential enemies out there is the word processor," he says. "Clinical staff could introduce something from another template — sometimes we'll see an entire paragraph from some other protocol that just doesn't belong in the protocol that's being reviewed."

Quality assurance program

As a result, the group developed a comprehensive program aimed at ensuring that informed consent documents distributed across all its cancer trials accurately describe the trials and contain all of the essential elements of informed consent.

Cronin describes several steps to this quality assurance program:

• Before each group protocol is even distributed to participating sites, the NSABP cooperative group leadership examines the informed consent template to ensure that it accurately reflects the details of the trial.

• Cronin says that once the protocol has been released, the NSABP's division of regulatory affairs makes staff available to address changes that local IRBs want to make to the informed consent.

"They will either talk with individuals from the IRB or talk with coordinators or doctors from our participating sites to enable them to relay the information to the IRB," Cronin says.

He says changes generally are approved as long as the intent of the protocol isn't affected.

• The NSABP carries out an intensive review of the consent forms for the first 100 subjects enrolled in any new clinical trial. Not only are corrections made, but problems that arise are shared with other institutional members to prevent them from making the same mistakes.

The goal of this step, Cronin says, is to intervene as soon as possible in the process, before too many subjects are improperly consented and the mistakes become more widespread.

• For each patient enrolled in any trial, a copy of the signed and dated informed consent document is maintained at the NSABP Biostatistical Center. This allows the group to check forms, but also keeps track of whether participants have indicated that they would allow further research with their biological samples, Cronin says.

"We allow patients to opt out of allowing their tumor specimens to reside in a bank and be used for future cancer research," he says. "By receiving the consent form, we can tell whether the patient circled 'yes' or 'no' for that. If we see that the patient does not want the pathology specimen sent (to the bank), we make sure not to send it out."

• Cronin says that while the NSABP conducts the triennial site visit audits of institutions required by the National Cancer Institute, its review procedures are more extensive than those required by the NCI.

In its reviews of local forms, Cronin says the NSABP doesn't just address how well the local forms conform to the template, but also how well they conform to their own institutions' rules. For example, the group will point out to local IRBs if a witness' signature is missing from a form.

"While we may not require a witness in the template, if the local IRB did, we want to make sure that the local rules are followed as well," he says.

Anomalies persist

Cronin says that in recent years, the work of the NCI's Central IRB has helped curb some of the problem of deviations from informed consent templates.

"Certainly for sites that accept the Central IRB version, which is in fact our version, the problem has gone down," he says. "At the same time, however, more new institutions have become involved. So I think it's in fact been a wash."

He says that overall, the rate of anomalies tends to remain steady. It's a problem he believes extends well beyond the NSABP membership, to other cooperative groups and multisite research ventures.

"I would have expected to see an improvement, but it still remains a problem," he says. "It hasn't gotten so good that we're willing to change our procedures."

While it may be possible for local IRBs to provide the type of intensive scrutiny of informed consent documents that the NSABP does, Cronin acknowledges that it's a question of how much staff time an organization can bring to bear on the problem.

"It's something we certainly don't expect to be done at a local level, mainly because of staffing issues," he says.