Who caused this tragic medication mistake?

A doctor who says she was wrongly blamed for a fatal overdose at a renowned hospital seeks her day in court.

By Mark Crane
Senior Editor

It was perhaps the most publicized drug overdose in history. A patient in an experimental breast cancer protocol received four times the already-high prescribed dose of the chemotherapy drug cyclophosphamide over a four-day period. For two months, physicians didn't even realize that the overdose had caused the patient's death.

Medication errors are hardly uncommon. But this one became a watershed event that roiled a national debate about patient safety. The mishap was exhaustively scrutinized by major media and was studied in papers and conferences by medical leaders across the world. The patient was Betsy A. Lehman, a 39-year-old health columnist for The Boston Globe. The hospital was the world-renowned Dana-Farber Cancer Institute.

"The reaction within medicine was: If such a preventable error can happen at an institution like Dana-Farber, it can happen anywhere," notes Martin J. Hatlie, president of Partnership for Patient Safety and a leader on preventing medical mistakes. "Celebrated failures often spark change, and this, coupled with the wrong-leg amputation case in Florida a few months later, became patient safety's Chernobyl. The Lehman case helped lead to the recognition that medical errors are most often caused by system-wide failures rather than by an individual who goofs."

The aftermath of the Lehman case still has medical leaders reeling. Virtually everyone in a position of authority at Dana-Farber when the mistake occurred in late 1994 is gone, including the institution's president, chief medical officer, financial leaders, and many department heads. Massachusetts health officials and JCAHO teams found dozens of deficiencies.

Few at the hospital were spared withering criticism. Many research projects ground to a halt while Dana-Farber officials instituted corrective measures and new policies dedicated to patient safety.

Physicians were reported to the state Board of Registration in Medicine. Three pharmacists were also formally reprimanded, along with 16 nurses, leading to an intense debate among medical leaders about whether such rebukes prevent errors or simply drive them underground.

The patient's family received a confidential settlement from Dana-Farber, described in The Boston Globe as being a "multimillion-dollar sum," to satisfy a wrongful death suit. Ironically, Lehman's husband is a scientist employed by Dana-Farber.

A physician sues the hospital and a newspaper

Seven years later, the case may yet return to the headlines. An oncologist, Lois J. Ayash, who had been the author and leader of the experimental protocol, has charged in a lawsuit that Dana-Farber scapegoated her. Ayash claims that confidential peer review material was leaked to the press, harming her reputation. She also alleges that she was wrongfully terminated and defamed, while male members of the protocol team were protected. Ayash is presently a clinical associate professor of internal medicine at the University of Michigan Comprehensive Cancer Center.

She also sued The Boston Globe and its former veteran medical reporter, Richard A. Knox, for libel. Ayash charges that the newspaper erroneously stated in March 1995 that she had countersigned the Lehman medication order. Although Ayash was protocol chair, she wasn't the patient's attending physician at the time. The newspaper did print a correction, but it was more than two months later.

Ayash also charges the Globe with violating her privacy by reporting on secret peer review hearings and her investigation by the state board.

Earlier this year, a trial judge in the libel case found for the doctor because the newspaper refuses to identify confidential sources who had provided information about the overdose and the hospital's peer review efforts. The judge, who didn't rule on the merits of the case, found in Ayash's favor because the Globe and its reporter have hindered her efforts to prove her case against Dana-Farber.

At one point, the judge threatened to impose massive fines against the newspaper until it revealed its sources, but an appeals court stopped him. No date has been set for a hearing on monetary damages. The Globe has vowed to appeal. Meanwhile, Ayash's case against Dana-Farber is also pending. The hospital has filed a motion to dismiss the case, but that probably won't be heard until the fall, say attorneys.

The rhetoric in the case has been vitriolic, to say the least. A Boston Globe editorial accused the hospital of missing an error "so glaring that any first-year medical student should have spotted it." A columnist wrote that the overdose errors "would make The Three Stooges look like brain surgeons," and characterized the mistakes as "nothing less than criminally negligent homicide." At the time those words were written, Ayash was the only physician who had been identified by the Globe.

The hospital and Ayash have used equally florid language in their legal papers. Ayash charges that the hospital's former physician-in-chief, David M. Livingston, made her "a scapegoat in hopes of protecting his own position and reputation," along with those of male colleagues. The hospital termed one of Ayash's allegations "paranoid," described some of her actions as "negligent," and said other members of her protocol team don't trust her anymore.

The case contains the most contentious issues in medicine and law: charges of political influence, how regulators should deal with health professionals who make honest mistakes, the confidentiality of the peer review process, the rights of a free press vs an individual's right to privacy, and simple miscommunications and faulty assumptions that can weaken a crucial link in the chain of care.

Four times too much medication is administered

In the fall of 1994, Dana-Farber was conducting an experimental protocol involving women whose breast cancers had not responded to traditional treatments. The protocol involved testing the efficacy and safety of high doses of cyclophosphamide in conjunction with cimetidine and stem-cell transplants.

In mid-November, a research fellow on the team apparently misread the protocol, and erroneously ordered a fourfold overdose of the chemotherapy drug for Lehman and another patient, according to court documents. Lehman suffered a severe reaction, but she recovered and was about to be discharged when she suddenly died. The other patient suffered severe toxicity and was transferred to an intensive care unit, but survived. She died two years later of breast cancer.

Ayash and other physicians thought, at first, that both patients had suffered a toxic cardiac reaction to the drugs because of the high doses. Ayash initially noted that it is extremely uncommon for bone marrow or stem-cell transplants themselves to cause such a sudden death.

It wasn't until February 1995 that a data manager at Dana-Farber discovered the overdoses. The hospital suspended the clinical privileges of two physicians (not Ayash) who'd been directly involved in the patients' care at the time. On March 31, one week after The Boston Globe published its first article in which Ayash was identified as the leader of the team, she was reassigned to administrative duty. She became the subject of two hospital internal investigations and an inquiry by the state board.

How did the overdoses occur, and why did it take so long to find out? Much of that is in dispute. There is evidence that some members of the clinical team questioned the size of the dosage, but didn't prevent its administration because of miscommunication and mistaken assumptions that others had already determined it was correct. An initial hospital investigation found that the protocol document, approved by Ayash, was "confusing and incorrect in the schema and in the area of the protocol specifying required data."

Around March 31, chief physician Livingston initiated a "corrective action" peer review proceeding against Ayash. She ultimately received an oral reprimand for her failure to find the overdoses earlier and for a "vague and confusing" schema.

In October 1995, Dana-Farber issued a press release about its investigations, including a list of dozens of actions it had taken to correct the problems that set the stage for the overdoses. It noted that several physicians and personnel from other departments shared responsibility for the error.

The press release criticized Ayash, though it didn't name her. The committee "concluded that this individual bore partial responsibility for the ambiguous nature of the protocol schema. This ambiguity contributed to the accident. Further, the manner in which this physician investigated the incidents contributed to the delay in detecting the overdoses. The principal investigator had not checked the written chemotherapy order with the protocol to determine whether there had been an overdose."

While the hospital didn't name her, the Globe did, and noted that she and the research fellow who administered the overdoses were under investigation by the medical board. The fellow, who had left Massachusetts to take a research position in England, later admitted that he had practiced negligently. The board suspended his right to renew his Massachusetts license for three years, but made the suspension retroactive, meaning that he can now reapply if he desires. No action was taken against Ayash's license, and the complaint is "completely closed," according to her attorney, Joan A. Lukey.

In February 1996, Ayash sued the newspaper and Dana-Farber, charging that she had been defamed and her privacy violated, and that her career had suffered as a result. Later that year, Dana-Farber announced that it planned a "reduction in force," and several doctors, including Ayash, were told they'd be let go. Ayash charged that she was dismissed in retaliation for filing the lawsuit, an allegation the hospital denies.

The physician states her case

Ayash's 44-page lawsuit against Dana-Farber and the Globe charges that the defendants tarnished her reputation in several ways. "She was the protocol chair but wasn't in charge of treatment on a day-to-day basis," says Lukey. "She did everything she could to figure out what went wrong, and berates herself constantly for not having figured it out sooner. Sadly, it would not have affected the outcome if she had."

Physician-in-chief David Livingston made several false statements, the lawsuit charges, including "the assertion that some clinical intervention might have been possible, when in fact there is no known antidote for a cyclophosphamide overdose; the assertion that she should have uncovered the cause of the tragic outcomes, when in fact she had no more responsibility, and significantly less opportunity before Ms. Lehman's death, to do so than did the treating physicians."

The lawsuit claims that Livingston told other colleagues that he believed Ayash engaged in a "cover-up" of the incident. "In fact, the hospital's preliminary report found no evidence of cover-up nor evidence of willful misconduct or malpractice," Lukey counters.

Livingston wasn't satisfied with the oral reprimand recommended by the corrective action proceeding, Lukey says. The chief physician wrote a memo to the hospital president that Lukey describes as defamatory. According to the lawsuit, the memo strongly implies that Ayash "knew of the overdoses shortly after their administration, but failed to do anything to save the life of Ms. Lehman," and that Ayash should have discovered the overdoses by careful chart review, "insinuating incorrectly that it was her sole responsibility to detect the overdose."

Ayash alleges that the Globe's reporter, Richard Knox, had access to confidential peer review materials that could have come only from someone at the hospital. She charges that four days after the article was published, Knox was aware of his mistake in saying that Ayash had countersigned the medication order. But the paper didn't print a correction until more than two months later. The retraction was too little and too late to ameliorate the injury to her reputation and career, she adds.

The suit says Knox's motives "included his desires to avenge the death of a professional friend and colleague, and his hopes of obtaining public recognition and acclaim for his 'investigative' series."

"The hospital denies that it knows who Knox's sources are, but that just isn't credible," says Lukey. "The hospital hung Dr. Ayash out to dry, the only woman on the leadership end of this team, while protecting the male physicians. My client became expendable."

The hospital fires back

Dana-Farber denies all of Ayash's allegations in an equally long legal brief, but notes that it is somewhat hamstrung because of the confidentiality requirements of the peer review process. It has released some documents to the court, under protest. The hospital denies that it leaked information to the newspaper or that the peer review process was unfair.

"Dana-Farber had an affirmative obligation to investigate the tragedy, learn from it, and develop policies and procedures to ensure that such a tragedy would not be repeated," the hospital notes in legal papers. "It was essential for any investigation to include review of why the overdoses were not discovered through the adverse event reporting system."

As protocol chair, the hospital contends, Ayash "was solely responsible for ensuring compliance" with its protocols, including reporting any adverse toxicities. "On Dec. 1, 1994, Ayash became inpatient attending for the month and reviewed [both patients'] medical charts. Ayash did not, however, check the chemotherapy dose orders or call the pharmacy to check whether these two patients got the correct doses. . . . Ayash admits that had she looked at the chemotherapy order forms she would have immediately recognized the overdose."

The hospital notes that Ayash admitted in depositions that she hadn't read Lehman's ECG, which had been taken the morning before her death, and that she should have been more aggressive in monitoring her potassium levels. Dana-Farber disputes the charge of gender discrimination, claiming its peer review actions were based only on the fact that Ayash, as principal investigator, was responsible for the conduct of the protocol and for filing adverse event reports.

The hospital notes: "Dana-Farber had a legitimate nondiscriminatory reason for its actions when she failed to adequately perform her responsibilities, including (1) writing an ambiguous schema; (2) filing three adverse event reports containing the serious inaccuracy that [the patients] had received the correct dose, and (3) [not checking] the dosing records" even after the suggestion of an overdose was raised at a pharmacology team meeting.

Ayash charges that team members refused to work with her because she'd been vilified by hospital leaders. Dana-Farber answers that her colleagues complained of her lack of collegiality and "voiced concerns that Ayash couldn't be trusted and was not a 'team player.' " Ayash also withdrew socially from her colleagues after the overdoses were discovered, the hospital adds.

The hospital also disputes that Ayash was ever terminated or that her privileges had been suspended. It argues that she voluntarily left the hospital at the end of 1996. Although she charges that the hospital's actions hindered her career, Dana-Farber argues that she currently earns more money than she did at the Boston hospital.

The Boston Globe has strongly defended its coverage and former reporter Knox, who now reports for National Public Radio in Boston. After the judge's ruling in favor of Ayash, a Globe spokesman said, "We have reviewed the decision and firmly believe that there are important journalistic and constitutional principles at stake. A newspaper's ability to protect the identity of its confidential sources is critical to the news-gathering function. We hope that these principles will ultimately be upheld on appeal."

Since the newspaper won't identify its sources, Ayash will have to build a more circumstantial case against the hospital, says her attorney, Joan Lukey. "We'll ask the hospital what precautions they've put in place so that only authorized information is released. Who holds that information?"

Attorneys expect that hearings on the Globe's appeal and Dana-Farber's motion to dismiss will begin in the fall. No matter what happens then, the one thing nearly everyone agrees on is that more appeals will follow.

 

Mark Crane. Who caused this tragic medication mistake?. Medical Economics 2001;19:49.