Survey of public information about ongoing clinical trials funded by industry: evaluation of completeness and accessibility

Introduction

No comprehensive system for tracking, organising, and disseminating information about ongoing clinical trials currently exists. Selected trials are instead registered in one or more of hundreds of distinct, predominantly online registers.1 The absence of a comprehensive, standardised register creates problems for clinicians2 and patients3 seeking information about ongoing trials and for reviewers preparing and maintaining systematic reviews. Because reviewers cannot easily identify all trials started on a given drug, reviews are often limited to published trials; if the published trials are not representative of all trials undertaken, the systematic review may be unreliable.4^–6 Clinicians who make treatment decisions based on biased systematic reviews or treat without the benefit of any trial evidence risk doing more harm than good.

We undertook a study to see whether information about trials of experimental drugs for prostate and colon cancer was available using online, US based trials registers.

Methods

We limited our evaluation to US based, phase III or phase II-III trials of drugs in development (hereafter referred to as phase III trials) for the treatment of either prostate cancer or colon cancer, the two cancers most heavily investigated by pharmaceutical companies.7 Phase III trials test drugs that have already shown safety and some efficacy in phase I and II trials respectively and are the final phase of testing new drugs before approval for use in patients. Phase III trials generally compare an experimental treatment with the current standard treatment or a placebo, involve relatively large numbers of participants, and, according to an Eli Lilly website statement from October 1999, include 90% of all patients and volunteers involved in drug testing.

Results

Discussion

No single pipeline information source listed all the drugs in phase III trials in our sample. In addition, the various pipeline sources often contained non-standardised and incomplete information, making it difficult to search for and summarise data about drugs in development. No one register, nor the sum of all included registers, listed every ongoing trial, with many trials identified in the pipeline sources not being listed in any of the registers. Pipeline source information sometimes contradicted information obtained from companies directly.

Searching several online registers to identify trials was cumbersome and time consuming, because of limitations in the organisation and search capacities of the websites and lack of standardisation and clarity of the language used to describe the trials. Some of the websites provided simply text lists of trial names; they lacked search engines and provided no groupings of trials by health condition. As a result, identifying trials required reading through all of the trials listed, or using the browser's “find in page” function to locate specific key words such as a drug name. Even if keyword searches could be performed quickly, they were not always reliable because of lack of standardisation of drug names and health conditions. Indexing trial listings using a thesaurus tree and a controlled vocabulary system such as Medline's Medical Subject Headings (MeSH) would theoretically ensure retrieval of the same set of trial listings, regardless of the “key words” used by searchers (for example, “prostate cancer” would map to MeSH “prostatic neoplasms”).12

The lack of standardisation—coupled with the frequent absence of information such as drug name, phase of testing, and condition treated—contributed to the difficulty of using the websites. Thus, the same trial listed on several registers varied in the amount of information available. A unique identifier numbering system would have helped confirm that similar listings referred to the same trial.13

Various efforts have been made by independent groups to address the problem, but none is completely satisfactory. We have developed an interim online resource to help improve access to information about ongoing clinical trials, called TrialsCentral (www.trialscentral.org),1 which links to hundreds of registers of ongoing US based trials. An international resource, Current Controlled Trials (www.controlled-trials.com), contains both a “register of registers” of controlled trials as well as a “metaregister of controlled trials,” a searchable database of information on thousands of ongoing and completed randomised controlled trials. The metaregister is perhaps the best effort so far, but it is still far from comprehensive. The Cochrane Collaboration14 has developed a database of published clinical trials available through the Cochrane Library.15

With the increasing recognition of the importance of registering ongoing trials,16^–18 several government supported initiatives have begun. For example, all trials funded by the UK NHS must be registered.19 In the United States the Food and Drug Administration Modernization Act 1997, section 113, requires prospective registration of all clinical trials of efficacy conducted in the United States for serious or life threatening conditions.20 In response to this act, the US National Institutes of Health has created its largest clinical trials database, ClinicalTrials.gov.21 However, even this database did not include trial listings for almost half of the 32 phase III drugs in our sample. Drug companies may not be willing to register their trials if registration is believed to compromise their commercial interests.

There is a pressing need for a transparent, comprehensive, and mandatory registration system for clinical trials. The best current sources of trial data are the institutional review boards or ethics committees, which theoretically have access to information on all initiated trials, at least in countries with such systems. Mandatory registration is the only sure route for obtaining information about ongoing and completed clinical trials funded by industry.22 Making this information available is critical to protecting the rights of human volunteers who contribute their lives to health research efforts, and critical to moving biomedical research forward at maximum speed.