Executive Summary

VITAMIN A OPHTHALMIC OINTMENT STUDIES VIOLATED federal regulations for the protection of human subjects, the National Institutes of Health concluded in its investigation of two studies conducted at the Massachusetts Eye and Ear Infirmary. The studies of the ointment for treatment of "dry eye" syndrome were conducted at the infirmary by researchers Scheffer Tseng, MD, and Kenneth Kenyon, MD. An investigation by NIH's Office of Protection for Research Risks (OPRR) found that the first vitamin A study had "departures from protocol," including changes in dosage, numbers of subjects and treatment regimen. The second study was "initiated without IRB ]institutional review board[ review and approval," NIH states. The IRB approved the study after it was already in progress. NIH is asking the hospital to conduct an "assessment of the adequacy of the informed consent process" used in the vitamin A study and to determine if any harm has occurred to the human subjects that were involved. The hospital also must "notify former subjects that their research participation occurred under conditions that did not comply with institutional policies or with applicable federal regulations," NIH stated. For the next three years, Tseng and Kenyon will be required to attach a copy of the NIH investigation to "any application or proposal" they submit for "HHS funding of human subject research." NIH began an investigation of the research after an article appeared in the Boston Globe in October alleging investigator conflict of interest and problems with human safety. Tseng and his supervisor, Kenyon, reportedly had acquired stock in the company that had purchased rights to the ointment they were studying. Tseng and Kenyon's vitamin A research is the subject of several other ongoing investigations by FDA, the Securities and Exchange Commission, the University of Miami and Rep. Dingell (D-Mich.). NIH's OPRR is ordering the infirmary to have its institutional review board "rereview" and reapprove all the infirmary's human subject research protocols, in order for the institution to qualify for HHS grant or contract support. The infirmary cannot accrue additional subjects to any of its 60 ongoing clinical research projects until the review board's analysis has concluded, NIH says. According to the hospital's vice president for Research Administration Albert Broseghini, PhD, all the IRB rereviews should be completed before April 1. On Oct. 19 Harvard Medical School issued a statement saying that Tseng had improperly conducted the vitamin A ointment research and that he had committed a "serious violation" of the school's conflict of interest policy. In November the National Eye Institute (NEI) suspended funding of two unrelated grants that had been awarded to Tseng and Kenyon. Tseng is currently affilated with the University of Miami; Kenyon is affliated with Harvard Medical School. NEI recently agreed to extend Kenyon and Tseng's awards, pending receipt of additional information from their institutions on the charges of scientific misconduct. NEI is also requiring that the institutions name interim principal investigators on the studies until NEI can make a final decision on the scientific misconduct issue. Johns Hopkins University recently concluded its own investigation of the vitamin A research. According to the NIH report, Tseng began his research at Johns Hopkins University School of Medicine in 1983, and later continued it at the Massachusetts Eye and Ear Infirmary. A Johns Hopkins release says its investigation found "certain institutional guidelines for the conduct of clinical research were not observed, and there were errors in the published report of the research." However, the advisory board of the medical faculty concluded: "There was no deliberate bias" in Tseng's research, "there was no evidence of conflict of interest, and most importantly, no patients were adversely affected."