THEME 1: SCIENTIFIC MISCONDUCT

CASE 2

From: Teaching the Responsible Conduct of Research Through a Case Study Approach: A Handbook for Instructors: With permission from the Association of American Medical Colleges

CASE Fl

Eric Woodworth is an oncology nurse working in a clinical research center (CRC) at a large academic medical center. Dr. Philip Thomas is an oncologist and clinician researcher who conducted a trial in the CRC of a drug being evaluated for its safety and efficacy in alleviating the nausea and discomfort associated with cancer chemotherapy. Eric assisted on Dr. Thomas's project in several ways. He attended to the patients' routine clinical needs and administered their cancer chemotherapy by I.V. He also gave the patients participating in Dr. Thomas' protocol oral doses of what may have been either the experimental drug or a placebo. The vials were numerically coded, so Eric did not know which he was providing. Finally, he interviewed patients concerning their symptoms, following a standardized questionnaire prepared by Dr. Thomas.

At times, Eric tried to guess, based on their responses, which patients were getting the placebo, and which were getting the real drug. In fact, he did not observe much difference in any of his patients and was convinced that the experimental drug was ineffective. He conveyed his opinion to Dr. Thomas, who merely shrugged and said, "We'll see."

After Eric's role in this protocol concluded, he was quickly engaged in other responsibilities. Meanwhile, Dr. Thomas compiled and analyzed the data that Eric collected and wrote up the results. Months passed, and the research ultimately was published in a well-known oncology journal. Eric was curious to read the results of this project, particularly since he was to be acknowledged for his contributions to the effort. Upon locating a copy of the journal, Eric read with astonishment Dr. Thomas's conclusion that the experimental compound was highly effective in alleviating the physical distress precipitated by chemotherapy. Eric read the article closely and decided that Dr. Thomas's recounting of the survey results was inaccurate, describing alleviations of discomfort that Eric never observed or recorded.

Questions for Discussion

1. If you were Eric, what would you do at this point to address these concerns?

2. Does Eric have a responsibility to take action toward correcting what he believes is an erroneous report?

Eric wondered what he should do in response. He hesitated to tell his supervisor, the head CRC nurse, because they did not have a very good relationship. Although Eric thought of himself as assertive and conscientious -- never hesitating to point out ideas for improving the operations within the CRC -- he understood that his boss viewed him more as a thorn in her side. He reported his concerns to her, nonetheless, figuring that, at worst, she would discount his report as another in a long list of complaints. As he predicted, his supervisor advised Eric that it would be in his best interest to focus on his current responsibilities and to stop looking for problems. That earlier project was so subjective, she added, that differing opinions on the results were not surprising in any case. Eric indeed recognized a certain subjective quality to the study, having wondered at times if he was recording patient reports consistently.

Questions for Discussion

3. Did Eric's supervisor respond appropriately to Eric's concern? How might you have responded were you in her position?

4. Having received such a response, what might Eric do next?

One day, when crossing the medical center complex, Eric ran into Dr. Thomas and expressed his surprise at the paper's findings. Dr. Thomas stated that once the survey results were decoded, a significant difference between patients receiving the placebo and the experimental drug became evident. Eric then stated that he would be fascinated to learn which patients were getting the drug and which weren't; he asked if he could take a look at the completed surveys now that they were unblinded. Acting hurried, Dr. Thomas stated that they had been sent to storage and that it would be too much trouble to retrieve them. He then dashed off. This behavior seemed suspicious to Eric and made him inclined to believe that some deliberate misrepresentation had taken place.

Questions for Discussion

5. Eric suspects that Dr. Thomas misrepresented the findings of the survey, but he cannot empirically support his suspicions without access to the surveys. Does he have a right to those materials since he is acknowledged in the paper?

6. Given Eric's lack of access to the surveys, how should he follow up on his suspicions?

7. Does Eric have an appropriate basis for lodging an allegation of scientific

misconduct? Is there a distinction to be made between an "allegation" and an "expression of concern"?

Eric tried on several more occasions to get the survey data from Dr. Thomas, without success. Knowing his supervisor was unsympathetic to his concerns, and upon the advice of a trusted colleague, he decided to approach the administrator of the medical center's institutional review board (IRB). The IRB reviews the ethical and legal ramifications of proposed clinical research and its administrator would certainly be interested in his suspicions, he reasoned.

Questions for Discussion

8. Does the IRB or its administrator have authority to deal with instances of scientific misconduct?

9. Whom would you approach at your institution if you suspected research misconduct?

Upon meeting with the IRB administrator, Eric explained his belief that Dr. Thomas had misrepresented the findings of his research. In response, the IRB administrator informed Eric that complaints of that nature should be taken to Dr. Holly Baird, the associate vice president for research and the institutional Research Integrity Officer. The IRB administrator counseled Eric that he should not take his concerns any further, though, unless he were fairly certain of them. His allegations seemed to be based on sketchy recollections of data collected long ago, she said, adding that, in her opinion, he did not have sufficient basis for a complaint.

Questions for Discussion

10. How should one decide whether a suspicion of wrongdoing is sufficiently significant to warrant lodging a formal complaint?

11. What are some considerations Eric might take into account in weighing whether to lodge a formal complaint?

12. In your opinion, does Eric have sufficient cause to register a complaint with the Research Integrity Officer?

After the conversation, Eric pondered different ways to handle this situation. One approach would be to lodge an anonymous complaint with Dr. Baird and simply let events run their course. Alternatively, he could present his concerns in person, but rather than focus on the inaccuracy of Dr. Thomas's work, he would simply assert a right to access the surveys. Both approaches seemed loaded with pitfalls.

Questions for Discussion

13. Should institutions encourage or discourage the practice of lodging anonymous complaints when individuals suspect misconduct? What problems might anonymous complaints pose for the institution? What issues of fairness might anonymous complaints pose for the accused? What advantages and disadvantages are posed by this approach for Eric?

14. If you were Dr. Baird, the institution's Research Integrity Officer, how would you handle an anonymous complaint?

15. Why might Eric's second idea, to focus on his desire to access the surveys, prove risky?

16. Would it be better for Eric or for someone else to examine the surveys? Why?

In the end, Eric approached Dr. Baird with the observation that Dr. Thomas's findings seemed inconsistent with Eric's knowledge of the surveys. He framed his concern as much as possible as an observation of fact, without suggesting that any deliberate misrepresentation had taken place. Eric was also quick to note that he repeatedly tried to access the original surveys without success.

Dr. Baird listened to Eric's report and told him that because he had questioned the integrity of Dr. Thomas' research, the institution would be compelled to explore the legitimacy of Eric's statements. This initial phase is termed an "inquiry" she said and would involve an initial review to determine whether a formal investigation would need to take place. Although the complaint might be resolved after reviewing the original survey instruments, it is possible, she explained, that an investigation might ensue, at which point Eric might need to become involved. Eric suddenly felt very queasy. Reflecting upon the prospect of having a face-to-face confrontation with Dr. Thomas, Eric wished that he had never raised the issue at all. The drug in question wasn't even that important, he thought. It's not as though patients would be harmed by it, he considered, wondering why should he take the risk of becoming further involved.

Questions for Discussion

17. Even if an investigation takes place, is it necessary for Eric to become involved in the process? Under what circumstances might his involvement be essential to permitting those conducting the investigation to arrive at a determination of what happened? Under what circumstances might his involvement not be required?

18. If Eric does become involved in the process, is it necessary for him to confront Dr. Thomas directly, as he envisions?

19. Should the clinical importance of the research weigh in the decision to pursue the allegation?

20. Eric might have wrongly accused Dr. Thomas. What should the consequences of that error be, if any?

21. If misconduct is found, what steps should the institution take?

22. If misconduct is ruled out, what steps should the institution take?

23. lf Dr. Thomas is exonerated, but Eric feels certain that he misrepresented the data, what recourse does he have?