What is the state of herbal clinical trial reporting?
The Declaration of Helsinki states that “every research study involving humansubjects must be registered in a publicly accessible database before recruitment of the first subject” (1).
Alan Levine Flickr, CC BY-2.0. “Open when we feel like it”.
However it is widely acknowledged that many clinical trials are not registered in a publicly accessible database, and that many results are not published at all (2). Of 224,000 study records on ClinicalTrials.gov only 23,000 reported results despite an FDA ruling for US research stating that results should be published within a year of completion, ‘The Final Rule’ (3). The #AllTrials campaign, part of the Sense About Science organisation, advocates for honesty and openness about clinical research and estimates that about half of the clinical trials carried out are never published in a journal, i.e. not only sharing the results but also the finer details of the study participants and methods.
Where to find clinical trial information?
A number of clinical trial registries exist where details of trials are publicly shared, and where the results can be uploaded and links to full publications listed.
https://clinicaltrials.gov (managed by the National Library of Medicine at the National Institute of Health (NIH))
https://www.ukctg.nihr.ac.uk (UK NHS)
http://www.who.int/ictrp/trial_reg/en/ (WHO International Clinical Trials Registry Platform)
http://184.108.40.206:8079/ctri/about-ctri/introduction-ctri (International Clinical Trials Registry India, WHO India)
There are probably others which I’ll list here in due course.
Professional guidelines for researchers
In the UK, professional bodies and societies advocate for transparency in clinical trial reporting. The Association of British Pharmaceutical Industry (ABPI) issued a new code of practice in 2012 on clinical trials transparency encouraging the registry of new trials and publication of results within set timeframes, and provide useful accompanying toolkits to assist researchers and trial managers.
The British Pharmacological Society ‘Pharmacology Matters‘ bulletin recently shared an article by Sile Lane from #AllTrials explaining how lack of rigor to publishing trial results leads to inaccurate evidence on which vital health decisions are made, and that patients and volunteers on clinical trials are being betrayed as their data is never used or reused.
How does herbal clinical research fair?
So for my field of research the golden question is what is the picture for Ayurveda traditional herbal medicine? This area of research is usually under even more intense scrutiny regarding the availability and quality of evidence. Also without pharma-scale investment, each piece of work is precious and adds to a much-needed evidence base.
I looked for all trials relating to ‘Ayurveda’ on ClinicalTrials.gov and sorted for all ‘completed’ reviews. The full dataset was downloaded into Excel as a .csv file (available here –> Ayurveda Clinica Trials BLOG). For this search term there were no results returned from NHS Gateway or WHO international registry.
In total, 18 studies were retrieved ranging from several Phase 2 (small scale human clinical trials) to others that were not categorised. Of the 18 studies that indicated they were ‘completed’, four updated their records accordingly instantly on the date of completion. The average time for records on ClinicalTrials.gov to be updated was twelve months, with the longest time for any further information to be posted being four years.
Only one trial indicated that the entry ‘has data’, meaning the authors have the option to share data on the system and/or provide a link to a full peer-reviewed publication. However, five others had shared results but not updated the system (below).
How many had published their results?
By searching for the unique identifier for each study (the NCTXXXX number) using Google searches and the PubMed database, the results from the clinical trials could be tracked down. In total, six had published their results in peer-reviewed publications. PubMed generally incorporates the identifier within the meta-data for each publication to help with retrieval of clinical trial information. Of these studies, all of the main outcomes were positive findings.
Therefore in this small sample, there was a publication rate of results of 30%, compared to a report rate of 50% estimated by #AllTrials.
Engagement with the clinical trials registry was poor with records updated slowly or not at all, and a tendency to not share study data and outcomes there.
By searching for the registered names of individual authors, it could be assumed that in a couple of cases, the researchers may have left their institution. Aside from that we do not know the motivations as to why indivituals and their organisations choose not to share the findings of their work.
Further work is needed to understand why researchers do not report their study findings, despite the clinical trials registry platforms such as that run by the NIH, NHS or WHO making the process simple. The question is who is ultimately responsible, the researcher, organisation, and how can full registration and reporting of trials be enforced? Also do all researchers from around the globe have access to technology infrastructure and have digital skills to utilise these systems in an equitable manner?
(1) WMA (2013). WMA Declaration of Helsinki. Available: https://www.wma.net/policies-post/wma-declaration-of-helsinki-ethical-principles-for-medical-research-involving-human-subjects/
(2) Mayo-Wilson, E., Heyward, J., Keyes, A., Reynolds, J., White, S., Atri, N., … & Ford, D. E. (2018). Clinical trial registration and reporting: a survey of academic organizations in the United States. BMC medicine, 16(1), 60.
(3) Zarin, D. A., Tse, T., Williams, R. J., & Carr, S. (2016). Trial reporting in ClinicalTrials. gov—the final rule. New England Journal of Medicine, 375(20), 1998-2004.