Andres T. Blei

Who owns the data

Recently, we received a letter from the principal investigator of a multicenter study, informing us of the withdrawal of their paper from consideration for publication. The study was an industry-sponsored study of a novel therapeutic approach for the treatment of hepatitis C. Receptive to well-performed early studies of new efforts in an area with dire therapeutic needs, HEPATOLOGY received the first version with interest. The reviewers pointed at the need to reach a different conclusion, pointing at the predominance of negative results and alternative explanations for the findings; the investigators thought the requests were reasonable. When the investigators contacted the sponsor, the pharmaceutical company did not accept such changes. Hence, the manuscript was withdrawn. So, who owns the data? The answer is simple. The law states the database is propriety of the sponsor. But the episode cannot be dismissed. A clash between proprietary and intellectual rights is most unfortunate, a conflict which runs the risk of being improperly resolved. At a time when many new therapeutic approaches are planned for the treatment of liver disease, the events illustrate the casualties of an approach that hurts all parties involved. (a) The pharmaceutical company has much to lose. The sponsor invested resources and energy to see protocols completed. However, unpublished studies do not advance the cause of a new therapeutic agent. Such decisions risk a loss of credibility within the hepatological community for claims of the drug’s effectiveness. Unable to attest to the purported benefits of the drug and having strained its relationship with the investigators, the pharmaceutical company will require renewed efforts and investment in order to establish the benefits of their approach. (b) The investigators also lose. They invested time and effort to carry out the study, a commitment ultimately rewarded by a solid publication. Obtaining the acceptance of a study in a peer-reviewed journal illustrates a certain quality of work and adds to the credentials of individual investigators. Thus, such publications require researchers to be involved in the planning, performance, interpretation, and submission of the research. Investigators who perform these steps wield intellectual property over the data.1 Commercial ownership of the database, although legally binding, cannot replace the impact of the intellectual analysis. (c) But the greatest casualties in this event are the patients. When humans volunteer to participate in clinical research, consent forms are signed and copies distributed. Underlying this contract is an altruistic motive that has fueled advances in clinical practice over many decades. The sense of satisfaction gained by participating in research studies is accompanied by a profound trust in the investigators who assume responsibility for the study. I imagine the dismay of patients, who having accepted the unknown risks of a new treatment, witness the shattering of their trust when their efforts are misspent. Nonpublication of data is a betrayal of trust.2 This discussion arises at a time of increasing scrutiny of the fate of nonpublished clinical studies. The International Committee of Medical Journal Editors has mandated registration of clinical trials by July 1, 2005, such that nonregistered studies will not be accepted for publication.3 HEPATOLOGY supports this statement and has agreed to institute such a policy. Its implementation awaits the designation of the registration site. We agree with the goals of full transparency in the publication of clinical research. At the same time, the situation depicted in today’s Corner highlights a limit for such policies. The sponsor has the legal authority to hold on to the data. But results obtained from human subjects cannot be viewed as simple pawns in a competitive environment. In fact, it has been recently proposed that research ethics committees assess public dissemination of results of clinical studies,4 extending their role to protect the rights of research subjects. With ownership comes responsibility. And responsible clinical investigation culminates in the presentation of data in peer-reviewed publications.

Advertising in hepatology

Habitual readers of the printed version of the journal, whose ranks may be dwindling in this era of electronic downloading, might have noticed a rise in the number of pages devoted to advertisements. Our statistics show a doubling of such pages over the last 5 years. The change reflects both the availability of more commercial products for patients afflicted with liver disease and the various health care choices faced by their providers. With the focus on newer therapies comes an additional editorial responsibility to oversee advertisements. During our tenure, a number of controversial examples have come to light, serving to underscore our thoughts and concerns. In the first instance, a drug company heavily advertised its product for correcting severe coagulopathy. While the drug received FDA approval for the treatment of hemophilia, liver disease was not included in the indication. The advertisement appearing in the journal avoided this restriction by stating the benefits of the drug for the treatment of hemophilia. Because of the high cost of the product and the anecdotal nature of the evidence supporting its use in liver failure, I contacted the company’s management, requesting a moratorium on such advertisements until results from large-scale studies in patients with liver disease were forthcoming. The company accepted the approach. Off-label drug use might be a widely accepted practice, but it should not be encouraged in the absence of data. In fact, a cautionary approach might also benefit pharmaceutical companies, as evidenced by a recent lawsuit attacking off-label drug use.1 In the second case, an advertisement promoting the benefits of drug A (produced by the company) over those of drug B (its competitor in the field of immunosuppression) was submitted to HEPATOLOGY. Several graphs illustrated the benefits of drug A when compared to drug B. This “competitive advertisement” mirrored the negative advertising found in the general media. While this strategy is likely to be effective, as well as recognizing that the public might benefit from an increased awareness of options,2 such advertisements are misplaced in a scientific journal such as HEPATOLOGY. The journal maintains high standards for the quality of the data printed in its pages, including the rebuttal of alternative findings. Advertisements should not contradict this principle. Given this commitment, we did not condone its publication. Our advertising pages, as well as those of many gastroenterologyand hepatology-oriented journals, have seen the promotion of an industry-sponsored clinical study aimed at comparing the effectiveness of two products, including one from the sponsor—for the treatment of hepatitis C—calling for recruitment of patients into the trial. The publication of the advertisement resulted in several complaints from readers whose criticism of trial design would render meaningless future conclusions of such a study. The editors lack the power to analyze the qualities of trial design in a one-page advertisement. We rely on the fact that such trials go through regulatory approval. Yet we cannot escape the fact that publishing the advertisement in HEPATOLOGY might provide legitimacy to trials whose main impetus lies in responding to market forces. In such studies, considerable efforts and resources are expended to demonstrate a competitive advantage over a similar product. Because of the potential for the perception of conflict with the mission of the journal, we will carefully scrutinize such advertisements in the future. More than a decade ago, it was concluded that 44% of advertisements in 10 leading medical journals would lead to improper prescribing if a physician had no other source of information.3 Since then, much has changed. Ten years ago in our field, therapeutic options for patients with liver disease were quite limited. More options exist today, and many more are expected in the next years, as the efforts of laboratory and clinical work come to fruition. The pharmaceutical industry plays an important role in this expansion, providing ideas, resources, and infrastructure for critical studies. Advertising is a legitimate tool to highlight the benefits of a product. At the same time, the principles of rigor applied to prove the benefits of the product should be extended to the quality of advertisements in our pages.