Publishing an exploratory trial can have a profound effect on subsequent clinical testing, the same way that a large-scale trial can profoundly influence drug approval and clinical practice. But similarly, it is difficult to argue that highly visible journals should lower their standards when evaluating clinical trials. The harsh criticisms that the FDA has experienced after reports of serious side effects of approved drugs are stark reminders of the need to constantly monitor safety. It would be absurd to argue that the preoccupation of regulatory agencies with patient welfare is unwarranted. This document highlighted the great deal of flexibility that existing regulations allow in the amount of data needed for the approval of an IND application, depending on the goals of the research, the specific testing proposed and the expected risks.īut despite this welcome flexibility, the emphasis is still on safety, as the document largely referred to microdosing studies designed to confirm that the expected mechanism of a drug's action can also be observed in humans, to measure binding affinity or localization of the compound, or to assess pharmacokinetics of the drug. Also, last January, the FDA issued the 'Guidance for Industry, Investigators and Reviewers of Exploratory IND Studies'. For example, the FDA has mechanisms to deal with clinical trials that use active comparators, acknowledging the ethical problems associated with some placebo-controlled trials. It would be unfair to say that regulatory agencies have not tried to be more supportive of clinical researchers.
Many reviewers, however, are not persuaded by this explanation and advise the journal against publishing the trial.
Nevertheless, we would be very reluctant to publish an exploratory trial that did not include efficacy data, and this is also true for other journals that publish translational studies.Īnother example of differences between the criteria of journals and the position of regulatory agencies comes from Europe, where ethical concerns prevent the approval of placebo-controlled trials if there is another drug that can act as 'active comparator'. Dosing and metabolism are often secondary endpoints and occasionally not even part of the submission. And the FDA definition notwithstanding, the primary endpoint of most of them is efficacy. Even more unfortunate, discrepancies of this sort are not all that infrequent.Īccording to the FDA, phase 1 trials “are designed to determine the metabolism and pharmacologic actions of the drug in humans, the side effects associated with increasing doses, and, if possible, to gain early evidence on effectiveness.” An exploratory clinical trial, in turn, can also provide pharmacological information but “is conducted early in phase 1, involves very limited human exposure, and has no therapeutic or diagnostic intent.”Īt Nature Medicine, we receive many papers reporting exploratory trials. Unfortunately for researchers, these divergent opinions can place them between a rock and a hard place. The problem was that when he presented his investigational new drug (IND) application to the US Food and Drug Administration (FDA), safety concerns forced him to change the trial design and reduce the number of subjects to receive approval.īoth the journal and the FDA have good reasons to emphasize different aspects of the trial-scientific accuracy and patient protection. The scientist was not complaining that the journal had been unfair with his work, and agreed that the trial had fewer than optimal patients. Apparently, the journal thought that although the results were encouraging, the number of patients enrolled in the trial was too low to draw definitive conclusions from the study. Last month, during a translational-research conference, a researcher complained that the New England Journal of Medicine had just rejected his latest clinical trial.