The proportion of trials ending prematurely has been decreasing steadily over the past decade. Our exclusive analysis shows that the clinical trial termination rate has fallen from 10.6% in 2010 to 4.7% in 2021. Such a trend can partly be the result of technology applications, digitisation, and changes in the trial space as decentralised clinical trial (DCT) elements are being incorporated more frequently into studies, says Priya Nair, senior clinical trial analyst at GlobalData. “A lot of DCT measures that are coming into place can help to overcome previous issues of enrolment, supply chain, or business measures,” she adds.
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By GlobalDataNair explains that sponsors are also focusing more on finding sites or CROs that are most appropriate for them and their trials. This includes specialist patient recruitment companies that help sponsors find the right patients before they consider terminating a trial, says Leanne Keem, head of operations and client relationships at Innovative Trials.
An ongoing trial terminates or is deemed as “terminated” when it stops recruiting or enrolling participants and will not start again. Clinical Trials Arena has established an exclusive taxonomic approach involving a review of thousands of drug trial public records to analyse different termination trends. Over 10 years of publicly available information and curated data were analysed in the Clinical Trials Database by GlobalData, the parent company of Clinical Trials Arena.
Terminations led by low accrual rates
The analysis shows that low accrual rate has been the most common termination reason from 2010 to 2021, comprising 25.4% of all terminated trials. Other reasons for termination were lack of efficacy (7.3%), adverse events (3.9%), business or strategic decisions (3.6%), financial (3.4%), and product discontinuation (2.7%).
Aside from a one-off increase in 2020 likely due to the Covid-19 pandemic, the rate of trial termination due to low accrual has been decreasing since 2010, reaching a lowest of 15.4% in 2019.
The decreasing prevalence of low accrual rate as a reason for termination may be a result of the more extended use of technology-aided solutions that make it easier for sites to recruit patients. Certain decentralisation aspects, such as home technology and certain tracking systems, make it easier to bring the trial closer to the patient and monitor them more closely, Nair notes.
Gabriele Brambilla, CEO of advisory firm Alira Health, says that social media has also played an important role in improving patient engagement, something that has slowly developed over the past few decades in the industry. “Now there is a new strategy and philosophy of involving patients much sooner, which creates a higher interest in participating in the study,” he adds.
There has been an increase in patient education and empowerment, Keem says. For example, sponsors put more effort and resources within the communities with the sole purpose of creating awareness to clinical trials and dispelling common myths, especially if sponsors are targeting diverse populations, she adds.
Oncology hit hardest by terminations
When it comes to therapy areas and recruitment, 32.6% of all terminated trials due to low accrual rate are in oncology, followed by central nervous system (CNS) with 14.2%. The complexity of the disease and clinical trial designs put a burden on recruitment. Keem says that oncology and CNS clinical trials focus on specific mutations, lines of treatment, or biomarkers in patients. Tight inclusion criteria shrink the pool of eligible patients, she adds.
The analysis also shows that low accrual rate as a reason for termination is most prominent in Phase II trials, representing 52.6% of all terminated trials due to low accrual in the last 11 years. The high proportion of terminations in this development stage is likely due to the investigational drugs being tested in actual patients with a disease, and the added inclusion criteria can narrow down the pool of eligible participants, Nair says.
Budget is also an important aspect in how successful the study will be. Brambilla says that Phase II trials have a lower budget than Phase III trials, and the cost of rescuing the study compared to the total cost of the study is much higher.
Industry becoming more transparent?
Another notable trend in the analysis is the proportion of terminated trials from 2010 to 2021 with no specific reason provided by sponsors for ending the trial prematurely (24.1%). The percentage of trials with no disclosed or available information as to why the study was terminated has been decreasing steadily over the past 11 years, dropping to 8.7% in 2021.
The Covid-19 pandemic accelerated the transparency between sponsors as they were more likely to share their experience and knowledge, Nair says. However, the altruistic transparency during the pandemic was only for the Covid-19 clinical trial pipeline, Brambilla adds. “There was this idea of creating an ecosystem of research to help each other out, but it wouldn’t happen for other therapy areas or indications,” he explains.
The rise in transparency is also likely linked to an increase in the number public companies, Brambilla says. A higher number of public entities create transparency because they are required to disclose the discontinuation of their clinical trials.
In 2015, the World Health Organization (WHO) released a statement on the public disclosure of clinical trial results. It highlights that researchers have a duty to report research results publicly, whether they are positive, negative, or inconclusive. In the UK, sponsors need to provide a brief explanation as to why they are terminating a trial early when submitting an end-of-trial declaration form.
On ClinicalTrials.gov, sponsors are provided with a free-text option to provide a reason for termination. However, a 2015 study found that “any number of reasons may be given for termination, and these need not conform to a controlled vocabulary”, resulting in hundreds of different entries.
The analysis also shows that academic institutions are most likely not to disclose the reasons why they are terminating their trials, making up 70.2% compared to 28.9% of company-sponsored trials. This boils down to how the trial is tracked,” explains Nair.
For example, institutions may not necessarily put the trial through a registry and keep all the information on their website. Rather than calling it a lack of transparency, Brambilla suggests calling it a lack of data entry, while industry sponsors will provide more information regarding their studies in the trial registries, press releases, filings, and news reports. “There are more people actively tracking that trial,” he adds.
Takeaways:
- The rate of clinical trial termination has decreased in the past decade. While the most frequently specified reason for termination is a low accrual rate, it appears that sponsors are benefiting from technology and patient engagement strategies to reduce recruitment issues.
- From 2010 to 2021, oncology and CNS were the therapy areas with a higher trial termination rate due to low accrual. The complexity of trial designs and tight inclusion criteria narrows down the eligible patient population.
- Industry sponsors are becoming more forthcoming about why they are terminating the trials. However, academic institutions are less likely to provide information regarding the premature end of their clinical research.
