Professionalism/Fishbein and the NIH

Background

In 1999, the NIH funded and conducted the HIVNET 012 clinical study in Kampala, Uganda. Its focus was comparing the transmission of HIV from pregnant mother to child between two drugs -- AZT and Nevirapine. The study concluded Nevirapine was more effective at decreasing transmission rates and was subsequently put on the market. In 2003, Johnathon Fishbein was hired at the NIH and found many issues with the study including improper record keeping, bad clinical practice, and under reporting of adverse effects. He claimed the trial should be invalidated. Fishbein publicized the case and was demoted and ultimately fired. After two years of battle over HIVNET 012, he was reinstated at the NIH despite the Institute of Medicine finding the study data valid. He is recognized for bringing to light serious allegations of systemic problems at NIH and is now regarded as a prominent whistleblower for exposing the truth.

Dr. Johnathon Fishbein

Johnathon Fishbein, an accomplished private-sector safety expert, was hired by the NIH in 2003 to improve the safety of its AIDS research. He had nearly 20 years experience in medicine with a specialty in pharmaceutical safety and oversight when he was hired as the associate director of the AIDS division at the National Institute of Allergy and Infectious Diseases. His job was “to create, implement, and enforce research policy in the Division of AIDS,” to ensure studies were being conducted according to ethical research standards.

HIVNET 012 Clinical Study

HIVNET 012 was a randomized, controlled trial of oral nevirapine versus oral AZT administered to 645 pregnant, HIV-infected women during labor, and to their infants during the first week of life. The study measured the number of new HIV infections in the infants. Women were randomly assigned to receive either nevirapine or AZT. There was no placebo group. The nevirapine regimen alone costed about $4 and was about 200 times cheaper than the long-course medicines used in the U.S. The study concluded that nevirapine was more effective than AZT at reducing HIV transmission.

Fishbein's Concerns

HIVNET 012 Study Flaws

When Fishbein first arrived at the NIH, his focus was on reviewing the 1999 African drug trial, HIVNET012. The study analyzed the effects of Nevirapine in pregnant women in Uganda. The drug had been around for 10 years but had toxic side effects including organ failure and bloody skin loss, both of which could be fatal. Fishbein found issues with the conduction of research during his investigation. The trial had bad record keeping, safety oversight, and did not follow good practice for human research protection such as informed consent. According to Fishbein, the major flaw in the study was the lack of reporting of “serious adverse events.”

The African Market

Kampala, Uganda has a high level of poverty. A large fraction of its citizens do not have access to food, clean water or medical supplies; therefore, the prevalence of serious endemic illness, including TB, cholera, sepsis and {[w:malaria|malaria]] is high. The researchers recording the data were not properly trained on assessing local conditions and did not record all adverse events. Accurate and detailed records of all events are vital to a clinical trial. An audit by the Westat Corporation in 2005 backed up the improper record keeping of the trial. Fishbein stated that “Africans are treated to a different standard than Americans...You can’t make determinations about drug safety this way."

In addition to the toxic side effects, over one half of the studied women became resistant in just one dose. Nevirapine was the only affordable antiretroviral drug available to many, thus, resistance proved lethal for women in the study. Fishbein believed it was unethical to focus on developing and marketing this drug because better, more effective drugs were available in the U.S.: “I think these people are used as guinea pigs. I feel that they're being used in a clinical research, and that's not being held to the same stringent standards as clinical research is here in the United States.” In 1998, while the HIVNET 012 was still underway, an ongoing study was conducted in the United States and Europe called Pediatric ACTG 316. It evaluated whether adding nevirapine to standard of care regimens will provide added benefit in preventing maternal-infant HIV transmission. The HIVNET 012 findings did not address whether nevirapine would give additional benefit beyond the standard HIV treatment and obstetrical practices used in the United States. To Fishbein, this demonstrating that Nevirapine was viewed and administered differently depending on location - Africa or the United States and Europe.

NIH

Fishbein wasn’t the first at the Division of AIDS to notice the flaws surrounding HIVNET012. “Flaws were common knowledge inside the division when I arrived,” Fishbein said. In 2003, Dr. Betsy Smith, a fellow NIH researcher came to the same conclusion. Her reports outlining the flaws had been rewritten and covered up without her knowledge by the AIDS Division Director, Edmund Tramont. Because of these events, Fishbein says that the division was “a management system guided more by politics than sound science,” and had “an atmosphere of intimidation” that inhibited the agency from correcting its many institutional flaws. Fishbein publicized the flaws but was met with resistance from leadership to make any reforms. He also witnessed bullying of researchers who disagreed with the department policy.

The NIH also never told the White House about the problems it found with the AIDS drug nevirapine before President Bush unveiled a $500 million plan to distribute the medicine across Africa in 2003. Fishbein believed the NIH covered up the issues because they had “reputations at stake”, and the “dire need to justify the billions of dollars that are appropriated to the division of AIDS for the research it sponsors.”

Appeals Process

Fishbein continued to voice his concerns but was met with an increasingly hostile work environment. After filling an official complaint with Edmund Tramont, the same person who covered up Dr. Smith’s concerns, he was demoted and then fired. He filed appeals with the Office of Management Assessment and Health and Human Services but the appeals were ignored. He then filed an Equal Employment Opportunity Commission complaint and a Whistleblower Complaint with the Office of Special Counsel. Finally, Fishbein brought the data to Congressman James Greenwood, Chair of the House Energy and Commerce Committee, hoping for a new, independent review. It was eventually Charles Grassley, the chairman of the US Senate Finance Committee, who picked up the case. Grassley stated “Retaliation against an employee for reporting misconduct or voicing concerns is unacceptable, illegal and violates the Whistleblower Protection Act." In January 2005, Fishbein testified before the Institute of Medicine Committee stating “gross violations of Good Clinical Practice in the conduct of the HIVNET 012 study rendered the data invalid.”

On April 7, 2005, The Institute of Medicine concluded “The AIDS medication nevirapine is effective and safe…[data] were well-supported.” The review was requested and funded by the NIH.

Conclusion

Fishbein and Professionalism

Fishbein’s professionalism and bravery not only are reflected in his decision to bring public awareness to the HIVNET study problems but also in his determination to continue research with HIV and AIDS. Jonathan Fishbein is an example of a professional who is willing to risk his career to maintain safe and ethical standards within the pharmaceutical industry. Fishbein did not give up trying to publicize the flaws he found, and sought support above his superiors. After his position at the NIH was terminated, he continued seek outlets who would look at his findings.

Fishbein strived to continue his work with HIV and AIDS research. According to U.S. National Library of Medicine (2018), Fishbein is a sub-investigator for several HIV/Aids clinical trials . Fishbein’s LinkedIn shows his latest position was as Senior Vice President of Safety and Medical Affairs/Commercialization Services with PRA health. At PRA health he continues to monitor the life cycle assessment of pharmaceuticals.

On the National Whistleblowers Center he was commemorated as the “one of the highest-ranking drug whistleblowers in American history" . His continued work with HIV/AIDS proves he was successful exposing malpractices to the public without sacrificing his career. He is successful because he persisted in the fight for what he believed was right. Social and professional pressures did not deter him from his goal.

Further Casebook Conclusions

Recommendations for future research in the Fishbein and the NIH casebook include investigating the workplace climate upon Fishbein’s return, determining any protocol changes within the NIH, and a case comparison.

Fishbein’s job was not reinstated immediately nor was he allowed to return to the HIV and AIDS research division at the NIH. He publicly disagreed with many of his superiors and colleagues, so it would be interesting to learn about the workplace climate upon his arrival back to the NIH. It is important for professional engineers to know how to mitigate the long-term consequence of whistleblowing. It would be beneficial to investigate the direct effect Fishbein’s allegations had on the protocol for both reporting unprofessional behavior and protocol regarding global clinical trials. Lastly, there is a benefit in comparing this case to other whistleblowers to shine a light on the gaps in Fishbein’s efforts as well as actions that should be exemplified.