A tragic clinical trial of an experimental hepatitis B drug thatled to the deaths of five patients and the initiation of threeseparate government investigations took a rancorous turnrecently with a flurry of heated letters.
Rep. Edolphus Towns, D-N.Y., chairman of the Subcommittee onHuman Resources and Intergovernmental Relations, wrote in aletter dated Oct. 21 to Health and Human Services (HHS)Secretary Donna Shalala that his subcommitteeUs investigationof the conduct of the Phase II trial of fialuridine (FIAU) Rhasraised serious questions of possible misconduct on the part ofemployees at NIH.S
FIAU is a nucleoside analog developed by OclassenPharmaceuticals Inc. of San Rafael, Calif., and licensed to EliLilly and Co., for the treatment of chronic hepatitis B. The drughad shown promise in preclinical and early clinical studies as apotent anti-viral agent for the disease. Trials using the drugwere terminated when patients in a Phase II study began toexperience adverse events.
Three investigations of the FIAU trial are now under way: aninternal review by the National Institutes of Health (NIH),which conducted the FIAU study; a formal investigation by theFDA; and a review of Rthe circumstances surrounding thedeaths and other adverse eventsS by TownsU subcommittee,part of the House of Representatives' Committee onGovernment Operations, which has jurisdiction over HHS and,by extension, the NIH. (A draft version of the FDAUs review ofthe trial is currently circulating at the agency and the finalreport could be available in weeks.)
TownsU letter to Shalala was precipitated by another letterwritten by the senior NIH investigator on the FIAU trial, JayHoofnagle. On Sept. 24, Hoofnagle wrote to inform PaulMelstrom, one of the patients from an earlier FIAU study, thathe would no longer be responsible for Melstrom's care.
Three days earlier, Melstrom had lambasted the NIHUs conductto an FDA advisory committee. Melstrom criticized Hoofnagleand other doctors at the NIH for ignoring toxic side effects ofFIAU that he experienced in a pilot trial done in spring of 1992.(The Phase II trial that resulted in five deaths began in March1993 and was terminated in late June. Melstrom was not apatient in that trial. However, one patient from Melstrom's trialdied after the study was completed. No connection to FIAU wasmade at the time, though his liver damage was similar to thatof the subsequent fatalities.
Melstrom said the NIH doctors were Rdismissive of patientcomplaintsS and were driven partly by career ambitions inconducting the FIAU trials.
Hoofnagle called MelstromUs statements Rtotally inaccurate,inappropriate and abusive,S and he wrote to Melstrom, RInview of your opinion of us and of the care you received, it isnot appropriate for us at the National Institutes of Health tocontinue to provide you with medical care or advice.S
Melstrom sent a copy of HoofnagleUs letter to Towns as well asto numerous other public officials.
Towns wrote to Shalala: RDr. HoofnagleUs letter, withconcurrence from the DepartmentUs Office of General Counsel,appears to be a vindictive, retaliatory response to Mr.MelstromUs comments and not grounded at all on sound medicalpractice or ethics or NIH policy.S
He continued: RIt appears that NIH single-handedly has revisedthe presidentUs health-care reform motto from THealth CarethatUs Always There,U to THealth Care thatUs Always There asLong as You DonUt Criticize your Government Doctor.U How cananyone have faith in such a system?S
Towns asked Shalala to take immediate action to Rprotect allpast, present and future NIH patients from such retaliatoryaction by NIH employees because of open patient dissent andcriticismS and to Rreview the conduct of responsibleDepartment employees.S
Shalala could not be reached for comment on Thursday.
Ruth Kirchstein, acting director of the NIH, told the New YorkTimes last week that although she did not know all thecircumstances of the case, Ran action like this (HoofnagleUsletter) is not to be condoned. No physician should do that.S
Betsy Singer, a spokeswoman for the National Institute ofDiabetes & Digestive & Kidney Diseases (NIDDK), the NIHbranch that conducted the FIAU trials, told BioWorld thatHoofnagleUs letter to Melstrom represented a Rpersonalresponse, not an institutional response.S She said NIDDKDirector Phillip Gorden wrote a letter to Melstrom on Oct. 22apologizing for Rany misunderstanding created by Dr.HoofnagleUs letter of Sept. 24.S
RI want to assure you that it is not the policy or practice of theNIH to limit its services to patient volunteers on the basis oftheir public comments and that you will receive the sameopportunities for assistance from the NIH as other formerparticipants in the therapeutic trial for hepatitis B,S Gordenwrote to Melstrom. Singer said Melstrom has been assigned tothe care of NIDDK Clinical Director James Balow for furthermedical care, and that the two have already had severalconversations.
Neither Hoofnagle nor Melstrom could be reached for comment.
The Subcommittee on Human Resources and IntergovernmentalRelations, which began its FIAU investigation in midsummer,will continue to review the conduct of the trials and willconsider the full array of tools available to it in pursuing theinvestigation, including conducting public congressionalhearings if that is deemed appropriate.
-- Lisa Piercey Business Editor
(c) 1997 American Health Consultants. All rights reserved.