Funding for this trial is largely misspent money, it may produce misleading results, and it should be abandoned, he says.
Dr. Kopans has been an outspoken critic of the trial, describing it as a “huge waste of money” in comments made last year. Now he has set out his criticisms of the trial in an essay published in the October issue of Clinical Imaging, which outlines his objections and concerns for the first time in a peer-reviewed journal.
The Tomosynthesis Mammographic Imaging Screening Trial (TMIST) is comparing digital breast tomosynthesis (DBT), also known as 3-D mammography, with the older 2-D technology or full-field digital mammography (FFDM).
Dr. Kopans coined the term DBT and formerly held a now-expired patent on the first version of this technology.
“It could be argued that the imaging part of TMIST is a waste of valuable resources,” he writes in the essay.
The “imaging part” of the trial refers to the primary outcome measure and driving purpose of the trial, which is designed to learn which technology is better at finding – and reducing the rate of – potentially lethal “advanced” cancers.
These cancers include larger HER2-positive and triple-negative malignancies; those associated with positive nodes; and metastatic disease. These malignancies correlate with breast cancer mortality, TMIST’s principal investigator Etta Pisano, MD, of the American College of Radiology, has said in the past.
However, Dr. Kopans says that this surrogate endpoint is problematic. “TMIST will only investigate whether or not digital breast tomography results in a decline in advanced cancers, ignoring the fact that many women still die from cancers that are not advanced at the time of diagnosis,” he writes.
“Clearly reducing the rate of advanced cancers is not the only way that early detection saves lives. Lives are also saved by finding cancers at a smaller size within stages,” Dr. Kopans writes. He adds that DBT has been proven in observational cohort studies to find more smaller breast cancers than FFDM.
Dr. Kopans’ opinion that TMIST is largely a waste of resources is not shared by the National Cancer Institute. “We feel strongly that TMIST is a critical study,” an NCI spokesperson told this news organization.
Study power concerns
Another concern is that TMIST “may be underpowered,” Dr. Kopans writes. That concern arises in part from a recent review of TMIST by an advisory committee (that was prompted by low patient accrual rates), which proposed reducing the size of the trial. Dr. Kopans says this would result in “a reduction of the planned power of the trial.”
The NCI says that reducing the study size has been discussed but has not yet been implemented. “Any reduction in size would, of course, have appropriate statistical considerations in mind,” according to the NCI spokesperson.
Dr. Kopans’ concern about statistical power extends beyond downsizing the trial. An advanced cancer in TMIST is counted “if it occurs at any time while the participant is on study,” according to the NCI. Dr. Kopans says that is a problem.
“Since DBT cannot have any effect on advanced cancers in the prevalence year (they are already there), data from the first year (prevalence cancers are likely the largest number) will be unusable, and if used will, inappropriately, dilute the results,” he writes.
Dr. Kopans hopes that the investigators address the statistical power issues with the trial because, if not, “its results may be grossly misleading.”
