Hutch admits confusion to FDA, but doctors insist patients not harmed
Seattle Times staff reporter
But the doctors insist that none of the leukemia patients in the clinical trials had been harmed by the problems and that all of them had provided their fully informed consent before enrolling.
"Indeed, clinical trials have been encouraging, resulting in some of the highest reported cure rates for acute myelogenous leukemia," Dr. Dana Matthews of The Hutch and Dr. Janet Eary of the University of Washington wrote the Food and Drug Administration last week.
Matthews, the principal researcher in the experiments, and Eary, director of the UW's Division of Nuclear Medicine, who is working with Matthews, received letters from the FDA last year warning them about problems in the way three related experiments were being conducted.
Last June, the FDA placed what is called a "clinical hold" on the experiments. A clinical hold is an order to halt human experiments when the agency does not think, or cannot confirm, the studies can be conducted without unreasonable risk to patients.
The FDA inspected The Hutch three times last year, partly in response to a Seattle Times series about problems in past clinical trials.
The suspended trials are part of a federally funded $11 million, 13-year series attaching radioactive isotopes to blood cells to supplement chemotherapy and total-body radiation in destroying cancer cells in bone marrow.
The FDA charged that patients were misinformed about radiation doses and that doctors failed to properly report deaths and hospitalizations or to perform or document essential procedures.
The latest response from The Hutch echoed previously reported comments by center President Dr. Lee Hartwell and Clinical Director Dr. Fred Appelbaum that the problems were mostly paperwork errors.
"Many efforts were all underway to enhance procedures for the oversight and conduct of clinical trials before FDA's inspections," Matthews and Eary wrote in their formal response last week.
These changes include hiring an outside firm "to help monitor our clinical trials." The name of the firm was deleted from the copy of the letter The Hutch posted on its Web site.
In addition, the doctors, who declined interviews, wrote that they had approved all admissions and dosages and radioactive scans, although "not all of the monitoring functions were reduced to writing."
The doctors promised to change the research protocols and patient-consent forms by March 31 "to clarify and enhance the discussion of radiation doses and associated risk."
More than 70 patients have gone through the experiments already, and more than 50 are planned in the future, including Hutch-coordinated trials at two California research centers.
The dispute between the FDA and Seattle's renowned cancer center focused on patient-consent issues. The Hutch argued that patients knew a radiation dose range described as "e.g., 50-300 milliCurie" was merely an example and not the actual range. The FDA says at least 11 patients got higher doses than they had agreed to.
The Hutch says these patients all understood from one- to two-hour family conferences that the amount of radiation delivered through the blood would vary by individual and was not as important as the amount absorbed by vital organs.
Concerning the hospitalizations, injuries and deaths the FDA said were supposed to be reported faster, the doctors said they thought expedited reporting only applied to unexpected setbacks. Many setbacks can be anticipated in cancer experiments, they said.
"The experiences that were serious, life threatening or fatal were not 'unexpected' or were not associated with the use of the investigational drug, or both," the letter states. However, "we have now conformed our reporting practices to what FDA thinks is appropriate."
Matthews and Eary also said they already have stopped using correction fluid, markovers and pencil erasers to change data in their studies and henceforth would write with indelible ink and make any changes with a single strike-through, initialed and dated — as required by the FDA.
In addition, the doctors promised to collect all their data in a single database by Sept. 30, to cross-check the data by Oct. 31, and to finish a larger database by Dec. 31.
Last week's letter follows two earlier responses, which The Hutch declined to release, and a teleconference, which apparently did not satisfy the FDA.
The FDA now faces a wide range of possible actions from reopening the trials to disqualifying Matthews and Eary from further work.
The agency, citing confidentiality because of proprietary interests, declined to comment on the latest response letter.