A recent article in the Journal of Acquired Immune Deficiency Syndromes asked the question “Should Sponsors and DSMBs (Data and Safety Monitoring Boards) Share Interim Results Across Trials?”  At first glance it’s the kind of question to which most ethicists would quickly respond, “Of course.” or “Are you serious?” However in the discussion that follows the authors point out that some researchers feel that clinical research study results, even if there are significant ethical and safety concerns, should not be divulged during the study to anyone, not even if a similar study is being conducted by other investigators.

Data and Safety Monitoring Boards (DSMBs), also referred to as Independent Data Monitoring Committees, Safety Monitoring Committees or Institutional Review Boards (IRBs), have the responsibility of approving and monitoring all research trials involving human subjects that are sponsored by the US government to ensure sound science, protection of research subjects from harm and adherence to sound ethical principles. The complexity of clinical research and the dramatic increase in the number of research studies nationally and internationally has not made it easy for DSMBs and in fact has spawned some commercial for profit DSMBs (another issue for future thical considerations), but their responsibility remains to protect human subjects in accordance with international guidelines and US law. (ref:  WMA Declaration of Helsinki – Ethical Principles for Medical Research Involving Human Subjects)

Shah and colleagues state, “… DSMBs and sponsors have ethical obligations to disclose information to protect the safety of participants in other trials, depending on the magnitude of the potential harm to those subjects, the consequences of disclosure and whether there are alternatives for protecting subjects … preventing significant harm to subjects, even those in other trials, is generally a higher priority than the consequences of breaching confidentiality.” I agree!

Why then the question? Surprisingly, there seems to be some debate on this issue. Yet, I am unable to find any statement in any US or international ethical guidelines which place restrictions on the duty to inform of harm by those who have knowledge of the potential harm. Indeed in order to fully protect human research subjects all information must be taken into account – published, public and unpublished. DSMBs and funding organizations should consider this as one of their fundamental responsibilities in protecting human research subjects. Failure to do so could cause unnecessary and irreparable harm.

Shah and colleagues focused on ethical issues and cite a study that we previously identified as violating specific ethical principles.  The concurrence of ethical questions on the identical study but identify additional ethical issues increases the concern that some DSMBs are not properly informed, adequately constituted, sufficiently knowledgeable, or may have conflicts of interest impairing their ability to act as protectors of research subjects, especially vulnerable subjects in resource poor countries .

Shah et al. suggest that the question they pose is unprecedented. This is an odd interpretation of the circumstances given that most ethicists would interpret the question as being rhetorical and would argue that it would not be ethical to enter into any agreement between a sponsor and a DSMB if there were an understanding that issues of safety to research subjects could not be revealed. A fundamental principle of ethics and law is non-maleficence (do no harm) which ethically and legally can be interpreted as knowingly withholding information that could result in harm (the basis of product recalls). Sound informed consents assure research subjects that they will be informed of any possible harm before as well as during the conduct of the study. We therefore question whether a DSMB, as an allegedly independent and non-conflicted board designed for the protection of research subjects, could ethically or legally enter into a prior contract with a sponsor that limits the DSMB’s responsibility to protect human subjects.

Unfortunately, stopping a study because of known safety concerns may be costly. Studies involving thousands of patients can cost millions of dollars in loss of funds to corporate sponsors, investigators, salaries for supporting staff, and loss of overhead. But regardless of economic costs, the safety of the research subjects participating in the study must outweigh any issues of confidentiality and inappropriate agreements between sponsors and the DMSB. The scientists and physicians conducting the study have the obligation to immediately report any serious adverse effects to the sponsor and the DSMB, the DSMB has responsibility of determining whether or not the adverse events are serious enough to halt the study and to inform all necessary individuals including research study participants of the adverse events. The duty to warn must also be extended to any study that the DSMB, the study sponsor or the investigators have knowledge of that raises similar issues.

References

  1. Should Sponsors and DSMBs Share Interim Results Across Trials?  Journal of Acquired Immune Deficiency Syndromes 2012 –  Download pdf
  2. WMA Declaration of Helsinki – Ethical Principles for Medical Research Involving Human Subjects – Website
  3. An Open Letter To The Presidential Commission For The Study Of Bioethical Issues. October 2011- Ethics in Health.com