The World Health Organization (WHO) is calling on all medical studies that test treatments on humans to be registered, in order to make research more transparent and enhance the public’s trust in science.
Currently, the registration of clinical trials – scientific studies carried out in human participants – is voluntary. As a result, negative results in the early stages of a drug’s development can be kept secret. The WHO is urging research institutions and companies to register all clinical trials, including the earliest trials, whether they involve patients or healthy volunteers. It made its call as part of the International Clinical Trials Registry Platform, a major initiative aimed at standardizing the way information on medical studies is made available to the public. WHO is also recommending that 20 key details be disclosed at the time studies are begun.
The initiative seeks greater transparency regarding all clinical trials. The planned Registry Platform, however, will not be a register itself, but rather will provide a set of standards for all registers. It has not only standardized what must be reported to register a trial but is creating a global trial identification system that will confer a unique reference number on every qualified trial.
Currently, there are several hundred registers of clinical trials around the world but little coordination among them. Later this year, the WHO Registry Platform will launch a web-based search portal where scientists, patients, doctors and anyone else who is interested can search among participating registers for clinical trials taking place or completed throughout the world.
The issue at the heart of this matter is that selective reporting of trials does occur, and it distorts the body of evidence available for clinical decision making. The thinking is that a large body of collected evidence, consisting of many studies, provides the best basis for changes in medical practice. If certain trials are not revealed, then clinicians do not have all the information necessary to make the best choices. If all trials are registered in a public repository, then everyone in the chain of healthcare can evaluate the entire body of clinical evidence.
However, not everyone agrees this is a good idea. Since the policy will recommend registration of every “interventional study” (i.e. every trial for every intervention, whether marketed or not; whether randomized or not; and whether early phase or late phase), the registration process itself could act as a disincentive for doing many early studies. The information could, at best, be confusing and, at worst, later used as a club against drug companies. Phase I and other early studies have a different scope and purpose that later trials and so the results are not necessarily comparable to a fully prepared study. Since we would never rely on these studies to prove efficacy of a drug, why allow the use of this data against the drug companies?
In addition, there is concern that these new requirements could jeopardize academic or commercial competitive advantages if they apply to preliminary trials of new therapeutics. Similar concerns have been voiced about the requirement to disclose certain items–such as the scientific title of the study, the name of the treatment being tested and the outcomes expected from the study–at the time of registration. These disclosures could prevent drug companies from securing valuable IP rights for new formulations, methods of making the drugs, and new uses of the drugs.
The result is that drug companies may delay or forego certain early studies in favor or fewer, larger studies that will not necessary provide information in the patients’ best interest. More cost, less information. Not the best scenario.
Results reporting
What information does the WHO want out there? Once a trial is registered, full transparency and accountability requires that all of the trial’s results be made available to the public without any bias or selectivity in reporting. At present, there is no formal consensus on international norms and standards for results reporting. The international understanding is as follows:
- It is understood that trial results databases would be useful for multiple constituencies (clinicians, systematic reviewers, patients, policy-makers) and are intended to complement, not replace, peer-reviewed journal publication
- Results should be reported in at least as much detail as suggested for the ICH E3 format, with the WHO CT-UID added and the Conclusions heading removed
- If the results are reported to a database other than the trial register(s) for the trial, there should be mutual links between the results database and the trial register(s)
- Results should be available with at least an English summary, and should be available without charge (i.e., open access)
- As a general standard, trial results should be disclosed within one year of study completion (“study completion” to be defined)
- The sponsor/funder is responsible for ensuring that results are reported, unless the trial is unfunded, in which case the primary investigator is responsible.
We hope to see further discussion on this matter and better guidelines on which trials and information should be disclosed.
