Reassessing Eligibility Criteria to Boost Enrolment

Only 3% of cancer patients in the USA choose to participate in clinical trials.

For a disease that takes around 8.2 million lives a year, this is a concerning figure for researchers working to bring life-saving drugs to the market. With 85% of trials failing to retain enough patients, CROs are readdressing the way they recruit.

While patients cite many reasons for not participating in trials fear of side effects, and concern about inconvenience, one of the most interesting facts is an assumption that they don’t qualify.

Part of this is down to lack of awareness about appropriate studies. A Research!America poll found that 80% of patients consider a physician’s recommendation important to the decision-making process, yet only 22% of patients said that health care professionals had mentioned a trial to them.

Technology such as trial matching apps may help to counter this, offering patients comprehensive information about trials that suit their specific conditions and requirements, and prompting them to find out more.

However, this is also a call for CROs to reassess overly-restrictive eligibility criteria. While these criteria are primarily in place to protect unsuitable patients from unnecessary risk, and to ensure non-anomalous trial results, too many restrictions could put even eligible patients off applying, as well as yielding trial results that aren’t full representative of a patient population.

Once a drug is released onto the market, physicians will need to know how it might affect a broad spectrum of people, in order to make informed decisions about whether it will work for their own patients. Looser criteria will not only offer researchers a larger trial population, but a more varied one, improving the study’s external validity.

In many cases, eligibility criteria are duplicated from trial to trial as an afterthought with little thought being given to the nuances of the drug, and the sorts of populations it may one day be used for. In order to increase enrollment and create more applicable trial results, it’s necessary for CROs to give thought to trial-specific eligibility criteria as a fundamental aspect of trial design. Thought should be given to which criteria are “must haves” and which are “would like to haves”, and clear scientific reasoning should be outlines as to why certain patients should be excluded.

Common reasons for excluding patients from cancer trials include organ dysfunction, brain metastases, HIV, and a history of previous cancers. In many cases, these conditions could further compromise patients’ health during the trial process. Nonetheless, by excluding such patients we lose the opportunity to understand the effectiveness of a trial drug on patients with these comorbidities.

If these criteria are to be widened, however, they will need to be done so ethically, with extra assurance that patients with existing comorbidities will not suffer undue harm during the trial. Trials will need to be addressed on a more patient-by-patient basis, with individual differences taken into account at every stage.

Patients will also need to take this potentially added risk - along with researchers’ plans to avoid such risk - into account when making a fully-informed decision about participation.

An article on cancer trial eligibility in the New England Journal of Medicine suggests that CROs widen the goalposts in earlier clinical trials, accepting a broad spectrum of patients, and modifying subsequent criteria according to those initial results. This will remove some of the hard-and-fast rules about who is and is not applicable to the study, allowing researchers to define and redefine eligibility at each stage of the trial process.

This rethinking of eligibility criteria has been supported by the FDA, who have met with clinical trial sponsors to help critically evaluate common restrictions and move toward a broader and more accurate picture picture of a drug’s effectiveness in a true-to-life trial population.

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