The Dark Side of Clinical Trials Data-Sharing

By Mikkael A. Sekeres, MD, MS, and Brian J. Bolwell, MD, FACP

Opinion

On January 26, 2016, the International Committee of Medical Journal Editors (ICMJE) released a proposal to require authors of clinical trials published in one of their member journals – and these are the biggies, including The New England Journal of Medicine, the Journal of the American Medical Association, The Lancet, and Annals of Internal Medicine – to make publically available the de-identified, individual patient data underlying the results presented in the article itself, within six months of publication.

The announcement has led to a maelstrom of criticism, much of it from scientists lambasting the ICMJE for potentially opening the doors to so-called research parasites (those who conduct research on data generated by others), and even resulting in hundreds of comments on Twitter linked to #researchparasite.

At face value, the ICMJE’s proposal makes sense, in that it supports transparency in research and data- sharing. It also offers the opportunity to enhance the integrity of published research and promotes the ability of other scientists to develop and test new hypotheses.

But what much of this discussion ignores is the threat to patient privacy, and how this proposal will impact the ability to conduct cancer clinical trials. It may even threaten aspects of Vice President Biden’s Cancer Moonshot that focus on expanding access for patient to these trials.

Unwitting clues to identity

We are obsessed with protecting patient privacy in healthcare, particularly in the setting of clinical research, both because it’s the right thing to do, and because it’s the law, covered under the Health Insurance Portability and Accountability Act of 1996.

What would it take to compromise a person’s privacy? It turns out, not much. The Department of Health and Human Services reports that “the combination of a patient’s date of birth, gender, and 5-Digit ZIP code is unique for over 50 percent of residents in the United States.” In other words, the majority of the U.S. population could be identified with these three items alone.

Two out of the three – age and gender – are standard parts of any clinical trial that reports basic demographics of enrolled participants and outcomes for men and women. The third – zip code – can easily be extrapolated from the zip code of the hospital enrolling a patient in a study, as even a hospital as large as Cleveland Clinic derives 80 percent of its patients from surrounding Northeast Ohio. The ability to identify clinical trial participants increases when even limited information is cross-matched to other publically available sources, such as voter registration rolls.

Additionally, within cancer trials, the ultimate measure of a clinically meaningful benefit to an intervention such as treatment with a new drug is improvement in overall survival. This is measured from the time of diagnosis or enrollment in a study to the time of death or the study’s end. Introducing these dates to publically disclosed information further increases the likelihood that an individual can be identified, particularly if that person has a rare cancer.

Let’s take, for example, hairy cell leukemia, which is diagnosed in approximately 600 people in the U.S. yearly. Compare that to the 70 million people in the U.S. living with high blood pressure. A person enrolled on a clinical trial of, say, a new monoclonal antibody for this type of leukemia whose supposedly de-identified data is made publically available is much more likely to be detectible than someone with hypertension, who could more easily get lost in the shuffle of the one-quarter of the U.S. population with the same diagnosis.

A cost burden

Cancer clinical trials are also increasingly becoming smaller, for two reasons. First, the holy mantra of cancer research is “bench to bedside” — taking an exciting lab discovery, developing a drug based on it that targets a specific cancer, and bringing the drug to the bedside to treat a patient. Second, cancer clinical trials are moving toward enrolling patients with particular genetic mutations underlying their cancers. So even within the small population of patients with hairy cell leukemia, a trial may focus on those hairy cell leukemia patients with a BRAF mutation. These types of trials are frequently limited to a single cancer center, or at most a small handful of centers, and are often internally funded, at least in part.

Introducing a requirement that clinical trial data be made publically available requires infrastructure in the form of databases, computer servers and personnel, which adds to the price tag for these studies. At a certain financial inflection point, studies may not be conducted, even when they ask important research questions for patients who desperately need new therapies.

Patients’ dilemma

A final impact that disclosure of patient data will have on cancer research is on the unfair position in which we will be placing our patients.

Before a person enrolls in a clinical trial, he or she provides informed consent, acknowledging that the potential risks, benefits, personnel involved in conducting the study and alternatives to the study treatment have been presented in an understandable way. If public disclosure of data is required, it would, justifiably, have to be added to the informed consent process and our patients would face what amounts to a Faustian bargain: Agree to allow your data to be made public, or you cannot enroll in a clinical trial. It would be all or nothing, as an “opt-out” clause is not being proposed.

This is not the sort of choice we want to force people to make when they are about to undergo treatment for their cancer.

While we appreciate the scientific rationale for the proposal to make clinical trial data publically available, in the end it cannot trump the rights of our cancer patients to maintain their privacy, have a full range of clinical trials available, and make treatment decisions free of conflict.

Dr. Sekeres is Director of the Leukemia Program and Vice-chair for Clinical Research, Taussig Cancer Institute, Cleveland Clinic Cancer Center. Dr. Bolwell is Chairman, Taussig Cancer Institute, Cleveland Clinic Cancer Center.

Photo Credit: ©Russell Lee