The website \u201cClinicalTrials.gov\u201d has become the first stop for many of us who need to check on trial activity of a particular drug.\u00a0 All larger human Phase 2 – 4 trials are listed there in quite some detail.\u00a0 While companies sometimes shy away from publishing full entry criteria or primary study endpoints, there is plenty of information on timelines including expected study completion.\u00a0 There is also a section dedicated to reporting study results and the existence of a final publication.<\/p>\n
Having worked in industry for many years, I am very familiar with the publication process.\u00a0 For large multi-author articles, the process of writing and finalizing the result interpretation can be a challenge.\u00a0 Nonetheless, after unblinding, a final manuscript should be ready for journal submission within 6 months.\u00a0 Occasionally it may take up to 12 months but any further delay is hard to justify.<\/p>\n
In the US, submitting updated trial information on an ongoing basis is a federal requirement.\u00a0 Why then is it that so many large trials remain without publication and no results provided in ClinicalTrials.gov?\u00a0 \u00a0I am not referring to abstracts, posters or oral presentations which investigators and companies are always eager and quick to produce.\u00a0 I am talking about full-fledged study write-ups which provide detailed methodology and primary study results.<\/p>\n
This compliance issue is not new; it has come to the attention of the public several times already.<\/p>\n
Jones[i] selected large trials (>500 patients per study) and found \u2013 embarrassingly enough \u2013 a lack of full publications for 29% of them.\u00a0 For most, the ClinicalTrials.gov site had no information on study results either.\u00a0 When publications existed, it took a median time of 27 months from study completion to publication.<\/p>\n
Subtracting time for data cleaning and journal review and peer review process, approx. 18 months go by in the internal manuscript review process at the sponsor.\u00a0 This typically involves investigators, medical writers and several layers of company personnel, from Clinical to Drug Safety and Marketing.<\/p>\n
Surprisingly, NIH sponsored trials did not fare any better.\u00a0 Ross[ii] reported a lack of publication in 32% of trials.\u00a0 When published, it took an average of 23 months.<\/p>\n
Studies of this size are not sponsored by individual investigators.\u00a0 These are expensive, ergo well-designed trials and results \u2013 good or bad – matter.\u00a0 In the Jones paper, approx. 77% of trials without publication were industry sponsored, the remainder had government funding or support from organizations like NIH.<\/p>\n
Prayle[iii]<\/sup> reviewed ClinicalTrials.gov for compliance with federally mandated reporting\u00a0 timelines and found that only 22% of trials were in compliance.\u00a0\u00a0 The rest were not.<\/p>\n Vaccine trials follow the trend already outlined: rampant underreporting of results and delayed publication.\u00a0\u00a0 Upon review of Clinicaltrials.gov information and other databases as well, Manzoli[iv] also found evidence of selective reporting (i.e., in favor of positive results) in industry studies.<\/p>\n While delays are bad, certainly lack of publication altogether is unacceptable and inexcusable.\u00a0 Who is holding the \u2018stragglers\u2019 accountable?\u00a0 Is there a ClinicalTrials.gov \u201cwebmaster\u201d who reviews (and polices) the submitted information for gaps and identifies laggards?<\/p>\n FDAAA 801 clearly states that \u201cresults submission is required\u00a0\u201c.\u00a0 Indeed, there is a fairly stiff penalty for non-compliance.<\/p>\n In 2012, three US lawmakers took action and asked FDA commissioner Dr. Hamburg \u00a0whether the assertions made in the BMJ articles were correct and what enforcement actions were taken by FDA [v]<\/sup>.\u00a0 I am unable to find Dr. Hamburg\u2019s response but attempts to improve compliance and data transparency were made.<\/p>\n Unfortunately, the well-intended Trial and Experimental Studies Transparency (\u201cTEST\u201d) Act is currently stuck in the Subcommittee on Health and seems to be going nowhere.<\/p>\n Cui bono?<\/p>\n ———————————————————————–<\/p>\n [i] Non-publication of large randomized clinical trials: cross sectional analysis. BMJ\u00a02013;\u00a0347<\/p>\n [ii] Publication of NIH funded trials registered in ClinicalTrials.gov: cross sectional analysis.\u00a0 BMJ\u00a02012; 344<\/p>\n [iii] Compliance with mandatory reporting of clinical trial results on clinicalTrials.gov: cross sectional study.\u00a0 BMJ\u00a02012;343<\/p>\n [iv] Non-publication and delayed publication of randomized trials on vaccines: survey.\u00a0 BMJ\u00a02014;\u00a0348<\/p>\n [v] http:\/\/www.fdalawblog.net\/fda_law_blog_hyman_phelps\/2012\/02\/bmj-article-on-clinical-trial-reporting-foments-discontent-on-capitol-hill-our-1500th-post.html<\/p>\n","protected":false},"excerpt":{"rendered":" The website \u201cClinicalTrials.gov\u201d has become the first stop for many of us who need to check on trial activity of a particular drug.\u00a0 All larger human Phase 2 – 4 trials are listed there in quite some detail.\u00a0 While companies sometimes shy away from publishing full entry criteria or primary Continue reading And the Results are \u2026Pending<\/span>