Drug development crucially relies on accurately designed and well recruiting clinical trials. However, low accrual rates of clinical trials and unmet recruitment targets have been global attention points for many years. A 70-80% of all clinical trials do not meet their recruitment aims in time (Korn et al. 2010; McDonald et al. 2006), leading to a delay in the access to effective new drugs for all cancer patients. Intriguingly, while only 3-5% of all cancer patients participate in clinical research during their disease course (Murthy et al. 2004), 80% expressed interest to participate in clinical trials if informed by their doctor (Moorcraft et al. 2016; Zogby Analytics for Research!America 2017; Virani et al. 2011; Barrios et al. 2018). These conflicting numbers signal ample room for improvement in trial accrual.
The delay in clinical trial conduct due to low recruitment rates does not only lead to a significant loss of invested resources – financial and otherwise – ethical and scientific issues are also involved. Patients consent to and presume meaningful use of their data after, while premature closure of trials may lead to underpowered analyses and inability to draw reliable scientific conclusions.
SMS-oncology has therefore made the improvement of patient recruitment for clinical trials a spearhead for the upcoming years. A dedicated department of Patient Inclusion has been established and is led by Ms. Wendy Onstenk, MD PhD. This department will be involved in both the design and conduct of clinical trials to advise on and support in maximal patient recruitment from clinical sites. Review of study protocols regarding the implementation of study-related procedures into clinical practice and definition of patient population, including the in- and exclusion criteria, feasibility studies and active outreach to and support of clinical investigators are amongst the key services that will be delivered by the Patient Inclusion team.
Many barriers hampering patient accrual to clinical trials have already been identified (Denicoff et al. 2013; Barrios et al. 2018; Chhatre et al. 2018). However, adequate solutions to tackle these barriers are mostly lacking. Most attention has so far been given to patient-related barriers, for example in terms of communication between patient and doctor, improvement of trial awareness amongst patients and attention for patient hesitancy toward randomization or clinical research in general. However, barriers from the health care provider perspective seem to play an at least as important role in the low trial recruitment rates. The Patient Inclusion team will focus on both groups by offering support to clinical investigators to lower trial workload on the one hand and by raising awareness of clinical trials amongst cancer patients to open up discussions in the doctor’s room more often on the other hand.
Patient eligibility criteria can also greatly restrict patient recruitment. A fine balance has to be pursued between setting the criteria strict enough to guard patient safety and trial population homogeneity and loose enough to ensure optimal patient recruitment. Careful considerations during the design of the clinical trial should be focused to prevent the exclusion of patients for reasons that are of limited relevance to the drug investigated. For example, patients with a poor overall condition – oftentimes defined as an Eastern Cooperative Oncology Group (ECOG) performance status >1 – are mostly excluded from participation in a trial. However, when performance is defined by the cancer and not by co-morbidities, one may question the adequacy of this exclusion criteria. These patients may particularly benefit from new effective treatments and their performance status is then only expected to improve with clinical response. Also, the validity of excluding cancer patients with HIV may be questioned. In the time that HIV was a non-treatable disease causing a severely disrupted immune system and shortened life expectancy exclusion of this patient group from cancer clinical trials seemed justifiable. However, new antiretroviral therapies have greatly improved the prognosis of HIV-positive patients, turning HIV into a chronic condition no longer determining life expectancy over many forms of cancer. Patients with well-controlled HIV should therefore nowadays be able to participate in cancer clinical trials, especially when it concerns HIV-related cancers such as liver cancer, head-and-neck cancer and anal cancer.
In line with the above-mentioned considerations, as well as other considerations regarding for example the presence of brain metastases, the American Association of Clinical Oncology (ASCO) has developed a generic protocol template with modernized eligibility criteria. This template can be accessed and downloaded here. Following ASCO’s recommendations, the Patient Inclusion department will pay special attention to such eligibility criteria when reviewing a protocol and advise sponsors where criteria can be relaxed with as aim to maximize trial accrual.
About SMS-oncology: SMS-oncology is a full-service oncology CRO that in addition to clinical operations provides expert advice on oncology drug development. With our unique business model of integrating top-notch clinical operations and expert advice, we cover the whole path from trial design to the setup, management and completion of phase I to IV oncology trials. We are specialized in early phase, pediatric and immuno-oncology trials.
Contact information: Communication on topics, comments, thoughts and questions involving patient recruitment via email@example.com.
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