Information on scientific leadership and contact details are often missing from clinical studies lodged with the two leading public trial registers, a Canadian study has found.
The omissions are despite the standards set by the registers themselves, the Minimum Registration Data Set criteria developed by the World Health Organization (WHO), and the conditions imposed by the International Committee of Medical Journal Editors (ICMJE) for clinical trials that may be considered for publication in member journals.
The context for the study published in the open-access journal PLoS ONE is the statement issued by the ICMJE in September 2004. From September 2005, the Committee stipulated, all clinical trials would have to be registered at inception in a publicly accessible register if they were to be considered for publication in ICMJE member journals.
Developed by the WHO as part of an effort to promote global standardisation of trial registration, the World Health Organization Minimum Registration Data Set lays down a minimum set of requirements – 20 data items in all – that should be included in a clinical trial register.
These criteria, which have been endorsed by the ICMJE, include elements of the study management, design and objectives, such as primary and secondary sponsors, key inclusion and exclusion criteria, interventions and primary/secondary outcomes. They also mandate the listing of a “research contact person”, described as the “person to contact for scientific enquiries about the trial”.
The two biggest public trial registers meeting the ICMJE standards for trial registration are the International Standard Randomized Controlled Trial Number (ISRCTN) and ClinicalTrials.gov.
As the Canadian research team led by Melanie Sekeres of Toronto’s Kunin-Lunenfeld Applied Research Unit and Toronto University’s Department of Physiology notes in PLoS ONE, ISRCTN requires the principle investigator to be identified for all registered trials, along with contact information including name, address and e-mail (providing a telephone number is not compulsory).
Clinical Trials.gov asks for listing of a central contact and overall study official for each trial. The name, degree, role and affiliation of the “person(s) responsible for the overall scientific leadership of the protocol, including study principal investigator” must be specified for trials not associated with US Food and Drug Administration Investigational New Drug (IND) or Investigational Device Exemption (IDE) applications. Central contact information must include the person’s name, degree, telephone and e-mail address.
Accountability measure
As the researchers point out, an important component of accountability in clinical research is assigning responsibility for the conduct of trials to study ‘chairs’ or principal investigators, who assume the scientific leadership for the studies. “Linking a given trial to an individual as a matter of public record advances scientific integrity by ensuring such individuals are available to address any questions or concerns that may arise from patients, their physicians, or other researchers,” they comment.
Without this capacity, the researchers add, “accountability remains a concern. Moreover, this information can then be compared to the investigators listed as authors, thereby providing a mechanism for ensuring that those responsible for the trial’s conduct also assume public responsibility for the trial’s outcome.”
The research team reviewed clinical trial entries listing Canadian investigators in the ISRCTN register and ClinicalTrials.gov, delivering a sample of 1,388 entries in total – 142 of them from the ISRCTN register and 1,246 from ClinicalTrials.gov.
The main outcome measures were the proportion of clinical trials reporting valid contact information for the principal investigator (PI)/co-ordinating investigator/study chair/site principal investigator, as well as study contact e-mail addresses. These outcomes were then stratified by funding source, recruiting status and register.
In all, 1,033 or 74% of the sample listed the name of the study chair, PI, co-ordinating investigator or site PI. For study entries that reported recruiting status, these details were much more likely to be available when the trial was not funded or only partially funded by industry.
Of the 663 non-industry-funded trial entries, 659 or 99% provided information on principal investigator (PI)/co-ordinating investigator/study chair/site principal investigator, compared with only 239 (41%) industry-funded trials. All 95 trials partially funded by industry that reported recruiting status provided information on scientific leadership.
Little more than one third (n = 533; 38%) of the trial entries in the sample provided mandatory e-mail contact information. Once again, there was a marked disparity between industry-funded and non-industry-funded studies in this respect.
Of the 663 non-industry-funded trials that reported recruiting status, 340 or 51% supplied e-mail contact information compared with just 88 of 590 (15%) industry-funded trials. Among the 95 partially industry-funded studies that reported recruiting status, 69 (73%) included e-mail contact information.
Non-compliant
“Our results reveal that a substantial proportion of registered clinical trial entries are non-compliant with providing critical study e-mail contact information that is mandated by the registry,” Sekeres et al state. “Industry-funded trials were significantly less likely to both identify individuals primarily responsible for scientific leadership and to provide trial e-mail contact addresses. Studies that were no longer in the recruitment phase were also less likely to provide this information.”
The authors do acknowledge that clinical trial registration “is still in its infancy”. Therefore, “it is not surprising that in the months following the ICMJE’s September 2005 deadline for mandatory registration, quality issues have become apparent”, they comment. Around the time that the Canadian study was conducted, trial registries were “inundated with newly registered trials as a result of the introduction of compulsory registration”.
Nonetheless, the researchers say, the omission of scientific leadership and contact information from many registered trials is an important finding for “several stakeholder groups, including patients, healthcare professionals, and systematic reviewers with a vested interest in the successful development of clinical trial registers”.
While considerable effort has been made to improve the quality of reporting in primary studies such as randomised controlled trials, “many of these reports are published with incomplete information”, they note. “Systematic reviewers require the ability to communicate with the study authors to seek clarifications and/or additional data, making the need to contact investigators even more critical for unpublished studies.”
Mechanisms for improving compliance are needed to ensure that trial registration “continues in a manner that is consistent with the goals of WHO and ICMJE”, the authors suggest. Registers could consider withholding assignment of a registration identification number from trials with incomplete data fields or studies listing contact information that has not been confirmed as both valid and current.
“Additional adherence measures should be developed at a policy level among governments, ethics committees, and funding agencies,” they propose.
Involvement in a clinical trial “should be a matter of permanent public record”, state Sekeres et al. “Transparency must not be selective in nature.”
