Deep Brain Stimulation and the Neuroethics of Responsible Publishing: Title and subTitle BreakWhen One Is Not Enough

In 2004, the International Committee of Medical Journal Editors put forward a fundamental truth: “The case against selective reporting is particularly compelling for research that tests interventions that could enter mainstream clinical practice.”¹ There is perhaps no arena in medical research where the threat of selective reporting is greater than in the emerging field of deep brain stimulation (DBS) and neuromodulation. This intervention is now being studied² for the treatment of several psychiatric diseases such as treatment-refractory obsessive-compulsive disorder, major depression, and Tourette syndrome as well as behavioral conditions like obesity, violent behavior, and substance abuse.

Although the risk of selective publishing is by no means unique to DBS, this area is particularly vulnerable to bias because of an excessive reliance on single-patient case reports. Until cohort studies are routinely performed, the possibility will remain that only positive results will be published at the expense of negative data that might also have important implications.

Balanced publishing of results—both pro and con—is particularly critical because scientific articles concerning DBS attract prominent media coverage. Public and patient understanding of the risks and benefits of DBS is strongly shaped by media accounts. One study of US and UK media coverage of neurostimulation found marked enthusiasm for the clinical translation of DBS, wherein positive attitudes correlated with stimulating “miracle stories.”³

Such problematic reporting amplifies the biases of selective scientific publication, leading to unjustified hopes and naïveté about DBS-associated risks. Taken together, each poses a threat to the reliability of reported data and the sustainability of the nascent field.

The well-known problem of publication bias with overreporting of positive results and underreporting of negative results is already indirectly evidenced in this young field: several single-case studies have been published only because of interesting secondary effects, whereas the primary outcome effects were not achieved. For example, a case of unsuccessful DBS treatment of an anxiety disorder was primarily published because of concomitant remission of alcohol dependence,⁴ and another case of likewise unsuccessful treatment of obesity was primarily published because of enhancement of memory states.⁵ So what might have happened to all the other single-case DBS interventions for which the primary outcomes were not achieved and no interesting secondary effects were observed? Indeed, one investigator's secondary outcome might well be another's primary concern.

For several reasons, the tendency of selective reporting is highly problematic. First, individual psychiatric patients might have agreed to participate in investigative DBS with the hope—but no promise—of personal benefit and the desire to contribute to generalizable medical knowledge. If only positive results are published, the patient's aspirations are not completely realized. Second, the overreporting of positive results and underreporting of negative results lead to a distortion of available evidence that might harm patients⁶ : patients might undergo procedures that might not be justified if all data were available. Third, publication of only positive results can lead to duplication of effort. Research groups will reproduce studies not knowing that comparable efforts were to no avail. This squanders precious resources and exposes participants to unnecessary harm.

For these reasons, all single-case DBS studies should be registered in a comprehensive registry of initiated clinical studies (eg, in a clinical research database similar to ClinicalTrials.gov). The idea of a registry was recommended in the 1977 report on psychosurgery of the National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research. At that time, when most psychosurgery was occurring in private practices, a national registry was not mandated, in part because of the Department of Health, Education, and Welfare's concerns over its authority to directly regulate psychosurgical procedures that involved neither drugs nor devices and that occurred outside of a research context.^{7 - 8} The device-based nature of DBS research could create jurisdictional opportunities for the National Institutes of Health or the US Food and Drug Administration to require participation in registries as a condition of research funding and the granting of Investigational Device Exemptions.

Mandated or not, the data from this registry could inform other researchers, reviewers, psychiatrists, media, and patients about existing and concluded DBS studies.⁶ Such a case registry might not only help reduce possible harm but also increase benefit. For several rare diseases (eg, movement disorders or particularly mixed psychiatric diseases), no large-scale study results will be available soon; therefore, registries might provide a means for identifying and summarizing evidence for establishing a more profound basis of potential beneficial effects.

To further improve assessment of whether observed DBS outcomes are beneficial or not, this quantitative effort should be complemented by a qualitative effort that seeks to assess comprehensively the effect of DBS on quality-of-life measures.⁹ The need for such measures is illustrated by a recent study involving patients with Parkinson disease in which despite, or probably because of, a clear improvement in various outcome variables after DBS implantation, many patients were not happier with their quality of life. Some of these patients might have tormented periods in their marriages or fail to resume professional activities postoperatively.¹⁰

The experience of patients with Parkinson disease does not seem specific to that condition but can be expected after rapid symptom modification in any chronic life-determining disease, psychiatric or somatic. For example, a rapid improvement of major depression, obsessive-compulsive disorder, or addiction will change previous personal activities of daily living and social relations in a more drastic and rapid way than can be compensated for by the individual or by his or her personal surroundings. For instance, in a patient with Parkinson disease and in a patient with major depression (cared for by T.E.S.), comorbid personality disorders became evident after “highly successful” DBS treatments. This effect seriously complicated the following treatment and reduced quality-of-life measures to below the pre-DBS state.

Therefore, merely reporting symptom-specific scores might be highly misleading with respect to the true net benefit for the patient. More comprehensive outcome reporting is needed in DBS study designs and in follow-up assessments and should integrate broader biopsychosocial outcome measures like reintegration into family life, social and work environments, and psychosocial and global quality of life. Moreover, these data might be complemented with qualitative measures, particularly because changes in disease severity, comorbidities, and psychosocial life situations are more difficult to capture in psychiatric disease than in movement disorders.

While science and a democratic society thrive on the open exchange of ideas and a free press, those who are privileged to produce, assess, disseminate, or report new knowledge have a responsibility to place scientific work into proper context. Without a nod to censorship, investigators, journal editors, and journalists should try to help their readership understand the significance of published work. This effort cannot be done when authors engage in selective submissions of their work, editors fail to ask about contrary data, and journalists hype whatever outcome they have been given. In the Nichomacean Ethics, Aristotle wrote of the greater responsibilities of those with superior knowledge to act morally and make good choices precisely because they knew better. Those entrusted with the creation and dissemination of new knowledge should aspire to Aristotle's phronesis. This is a lesson that transcends the DBS example and is pertinent more generally for science and society.