By Ed Miseta, Chief Editor, Clinical Leader
A recent article on PLOS Medicine caught my attention. Titled, “Why Most Clinical Research Is Not Useful,” the missive, written by John Ioannidis, provides insights for all clinical executives to consider.
The term “clinical research” covers all types of investigation addressing questions of treatment prevention, diagnosis, or prognosis of disease. Clinical trials are the major design intended to answer these questions. If the clinical research is useful, that means it can lead to a favorable change in decision making—either by itself or when integrated with other studies and evidence.
Unfortunately, of the approximately one million papers on clinical research published to date, Ioannidis notes most are not useful. “Waste across medical research has been estimated as consuming 85 percent of the billions spent each year,” he says. Ioannidis then points out that most published research is false and more of it needs to be made true. His paper discusses prospects for improvement.
How Do You Make Research More Useful?
To make clinical research more useful, a good first step is defining what actually makes the research useful. Ioannidis states there is higher utility in solving problems with higher disease burdens. But context is also important. Problems with low prevalence but grave consequences for patients also delivers high utility, especially if the research can help develop treatments in other disease areas. Consideration must also be made for explosive epidemics, such as Ebola, which can quickly get out of control. At the same time, clinical research can deliver “dis-utility” when disease mongering causes a fictitious perception of disease burden in otherwise healthy individuals.
In defining useful research, Ioannidis notes it must provide a clinically relevant gain. In other words, it should create new learnings or add to what we already know. Research studies should be designed to provide sufficiently large amounts of evidence to ensure patients, clinicians, and decision makers can be confident in their knowledge of benefits and harms.
“Ideally, studies that are launched should be clinically useful regardless of their eventual results,” says Ioannidis. “If the findings of a study are expected to be clinically useful only if a particular result is obtained, there may be a pressure to either obtain that result or interpret the data as if the desired result has been obtained.”
The Role Of Pragmatism And Patient Centeredness
Other factors should also be primary considerations in clinical research. Ioannidis believes it’s essential for research to be pragmatic, meaning it should be applicable to real-life circumstances (e.g. the trial’s patient population should be representative of the general population). Deviating from real-life circumstances could invalidate the main conclusions of the study. Although no trial is ever a perfect random sample due to the consent process, Ioannidis notes pragmatism has long been advocated in trials. Unfortunately, clinical trial conditions also do not mirror real-life scenarios.
Useful clinical research is also patient-centered, meaning it is done to benefit patients or preserve health and wellness. It should be aligned with patient priorities, patient utility, and acceptability of the intervention. Ioannidis does see a renewed focus on patient centricity and points to the Patient-Centered Outcomes Research Institute (PCORI) as one example of this movement. But he notes patients are still rarely involved in setting research priorities.
Other factors that Ioannidis believes should be considered in clinical research include:
- Good value for the money, especially when resources are limited
- Feasibility (the study is not overly difficult to conduct)
- Transparency (study data, protocols, and other processes made available for verification)
Suggestions For Improving Research
With all of the factors that could reduce the usefulness of a trial, Ioannidis points out that blame should not be placed on specific groups. Instead, he recommends that these limitations be seen as opportunities to improve. These challenges involve not only researchers, but institutions, the industry, journals, and other stakeholders, including patients.
Ioannidis notes there are several steps the industry can take to make research more useful. An initial step toward improvement would involve better training physicians to understand research methods. Academia and companies in the industry could also encourage researchers to engage in clinically useful papers, and provide better pay for the work they perform.
Rather than having tension between pharma companies and regulators, sponsors should be encouraged to champion useful clinical research, with regulators matching commercial rewards to clinical utility for industry products. Ioannidis notes this would align the interests of shareholders with those of patients and the general public.
Finally, Ioannidis says “blue-sky science” (discovery research without prespecified deliverables) is important and requires public support. Journals can help by setting standards for acceptable research, and external groups could appraise the clinical utility of papers published in such journals. Since patients and advocacy groups have the most to gain by an increase in useful research, those groups could serve as a positive influence to useful research by becoming savvier about the science and putting aside biased influences.
“Reform and improvement are overdue,” adds Ioannidis. “Overall, not only are most research findings false, but, furthermore, most of the true findings are not useful. Medical interventions should and can result in huge human benefits. It makes no sense to perform clinical research without ensuring clinical utility.”