PTJ strives to improve its processes to enhance readability, simplify manuscript submission for authors, and ensure that only papers with a reasonable likelihood of publication proceed to full review—all with the goal of publishing high-quality, clinically relevant content. In particular, manuscripts reporting clinical trials must be prospectively registered in a publicly accessible trial registry before participant enrollment commences. Although PTJ has required clinical trial registration since 2008, the definition of a clinical trial continues to perplex some authors. Confusion may result in failure to prospectively register a trial, thus preventing PTJ (and many other journals) from publishing the study findings once the study has been completed.
So, what is a clinical trial? The National Institutes of Health (NIH) revised its definition of clinical trials in October 2014 in order to more clearly distinguish between clinical trials and clinical research studies.1 The NIH defines a clinical trial as “a research study in which one or more human subjects are prospectively assigned to one or more interventions (which may include placebo or other control) to evaluate the effects of those interventions on health-related biomedical or behavioral outcomes.”
The NIH considers prospective assignment (which may involve randomization but not necessarily) to be a predefined process specified in a protocol that stipulates the assignment of research participants (individually or in clusters) to one or more arms of a clinical trial. The NIH1 defines an intervention as:
… manipulation of the subject or subject's environment for the purpose of modifying one or more health-related biomedical or behavioral processes and/or endpoints. Examples include: drugs/small molecules/compounds; biologics; devices; procedures (e.g., surgical techniques); delivery systems (e.g., telemedicine, face-to-face interviews); strategies to change health-related behavior (e.g., diet, cognitive therapy, exercise, development of new habits); treatment strategies; prevention strategies; and, diagnostic strategies.
A health-related biomedical or behavioral outcome is defined as1:
… the pre-specified goal(s) or condition(s) that reflect the effect of one or more interventions on human subjects' biomedical or behavioral status or quality of life. Examples include: positive or negative changes to physiological or biological parameters (e.g., improvement of lung capacity, gene expression); positive or negative changes to psychological or neurodevelopmental parameters (e.g., mood management intervention for smokers; reading comprehension and/or information retention); positive or negative changes to disease processes; positive or negative changes to health-related behaviors; and, positive or negative changes to quality of life.
Increasingly, PTJ receives manuscripts describing clinical trials where the intervention is directed at the therapist, and therapists rather than patients are assigned to the intervention groups (eg, a trial evaluating the efficacy of an education intervention designed to improve physical therapists' knowledge about a particular condition). These types of trials may measure outcomes at the therapist/provider level rather than at the patient level. Although these studies are considered clinical trials, it is the trial outcomes that determine whether prospective registration in a trial registry is required.
PTJ has adopted the approach of the International Committee of Medical Journal Editors,2 which states that “if the purpose of the trial is to examine the effect of the provider intervention on the health outcomes of the providers' patients, then investigators should register the trial. If the purpose is to examine the effect only on the providers (for example, provider knowledge or attitudes), then registration is not necessary.”
What does prospective registration of a trial entail? Prospective clinical trial registration involves documenting the protocol in a trial registry prior to the first participant being enrolled. Clinical trial registration is important for a variety of reasons. Registration overcomes problems of selective reporting (where researchers report only favorable results from clinical trials) and publication bias (where trials with favorable or significant results are more likely to be published than those with negative or nonsignificant findings). Prospective registration also helps minimize needless duplication of trials by alerting researchers to trials that are already underway.
The International Society of Physiotherapy Journal Editors (ISPJE) endorses a policy of mandatory prospective registration of clinical trials in a public trials registry as a condition for considering a manuscript for publication.3 PTJ was one of the first physical therapy/rehabilitation journals to implement such a policy and has required prospective trial registration for trials that commenced participant recruitment after January 2009. Trial registration is not only an issue of good research practice; it also is consistent with ethical principles outlined by the Declaration of Helsinki,4 which advocates that research studies involving human subjects are registered in a publicly accessible database before enrollment of the first subject. In most countries, the codes of conduct governing research require investigators to conform to the Declaration.
Although registration of clinical trials published in physical therapy journals is increasing, only 48% of clinical trials published in 2012 in physical therapy journals were registered,5 showing that the profession still has quite a way to go. BMJ recently highlighted the lower registration rates for trials of nonregulated interventions compared with the registration rates of trials of regulated interventions6 and called for improved transparency in clinical trials of nonregulated interventions. Over the past few months, the PTJ Editorial Board has reviewed both our policies governing registration of clinical trials and our instructions to authors on the PTJ website. As a result of this review, we have implemented changes that we hope will assist researchers in deciding whether their study requires prospective registration in a clinical trials registry:
As of July 1, 2015, PTJ has adopted the NIH definition of a clinical trial and has adapted the NIH clinical trial decision tree to assist researchers in determining whether a study is a clinical trial, and, if so, whether it needs prospective registration (Figure). Going forward, the Editorial Board will use this decision tree to decide whether a manuscript should be classified as a clinical trial. See examples.
For manuscripts submitted July 1, 2015, and thereafter, PTJ requires all clinical trials with patient-level outcome measures to be prospectively registered in a trial registry. Such clinical trials that have not been prospectively registered will be rejected at prescreening. See examples.
We hope that our authors and readers continue to support PTJ's efforts to ensure that clinical trials are conducted and reported according to best practices, including a publicly available, prespecified trial protocol. We encourage authors to visit the World Health Organization's trial registration site7 for guidance in how to register a trial or identify an appropriate trial registry.
Decision tree for clinical trials and trial registration. Adapted from the National Institutes of Health.1
Appendix
Clinical Trial Registration: Case Examples
- © 2015 American Physical Therapy Association
