As the pharmaceutical industry evolves, a rising trend appears in clinical trials. Progressively more pharmaceutical companies adopt smarter and unconventional trial designs for their investigational therapies.
Three reasons why the industry had to rethink the clinical trial designs
1. The urgent need to deliver new medicines quickly
The COVID-19 pandemic urged pharma to rethink clinical trial design and create a global network of partnerships to accelerate innovation while ensuring trial integrity and data validity are maintained.
2. The barriers to the conduct of RCTs in certain disease types
Certain disease types cannot support the usual design of a randomized controlled trial, such as in novel drug targeting (e.g., gene-fusion targeting in tumor-agnostic therapies).
3. The limited patient availability
Currently, a considerable percentage of trials fail to meet their enrollment goals, sometimes leading to significant delays in their completion.
Designing trials for Rare Diseases, for example, comes with challenges related to a quite limited and geographically dispersed patient pool and difficulties identifying the most suitable trial population.
The obstacles observed in conventional clinical trial design types in recruiting and retaining patients call for more adaptive trial designs.
Which are the most usual types of Unconventional Trial Designs?
1. Adaptive Designs (AD)
Compared to the traditional ones, adaptive designs in clinical trials utilize data accumulating during the trial to modify the course of the study, following pre-specified rules.
According to Thomas Jaki et al., 2018, some of the pre-planned changes we may see during this type of trial are:
- refined sample size
- abandonment of treatments or doses when necessary
- modification of the allocation ratio of patients to trial arms
- identification of patients who are most likely to benefit and focusing recruitment efforts on them
- Trial completion at an early stage for success or lack of efficacy
We see these designs across all phases of the clinical process, from the early phase to confirmatory trials.
The benefit of these types of design is that they best utilize the trial resources, requiring less money, less time, and fewer participants. At the same time, the results can often be more efficient and informative than those of traditional studies.
2. Complex Innovative Trial Designs (CID)
These are “highly innovative trial designs for which analytically derived properties may not be feasible.”
Launched in August 2018 by the US FDA, the CID Pilot Meeting Program aspires “to support the goal of facilitating and advancing the use of complex adaptive, Bayesian, and other novel clinical trial designs.”
3. Master-protocol studies
Initially designed for oncology research studies, master protocol trials simultaneously evaluate more than one investigational drug and more than one cancer type within the same overall trial structure, saving valuable time and effort.
4. Decentralized clinical trials
Decentralized clinical trials allow remote data collection using tools such as apps, sensors, wearables, online diaries, and video dosing confirmation.
The rise of digital technologies enables patients to receive treatment without traveling to a research facility.
As the patient receives the treatment in their natural environment, this type of study comes very close to real-world research applications.
Janssen: Notable player in the space to join the game of unconventional trial designs
1. Sponsored an at-home-based study on a wearable that detects AF
One of the emerging pharma players in the unconventional clinical trial design space is Janssen. Back in 2018, Janssen sponsored an at-home-based study of 2,659 volunteers, called mSToPS (mHealth Screening To Prevent Strokes), to evaluate a wearable electrocardiogram patch as a novel way to detect remotely atrial fibrillation (AF).
According to the study results, patients with asymptomatic AF were diagnosed earlier with the patch than those who received only routine medical care.
2. Reduced logistical and administrative pain points for patients participating in trials
Janssen has also incorporated a digital technology platform called iSTEP (Integrated Smart Trial & Engagement Platform) into a Phase 2 registrational clinical trial to help patients overcome logistical and administrative challenges common in clinical studies.
The platform tracks medication kits, from arrivals to allocation and dispensing to returns.
Moreover, it provides the patients with customized information like dosing instructions and tutorial videos that previously used to come in booklet form.
It includes electronic drug labels in the patient’s preferred language that are updated immediately in case of protocol changes, even after the trial initiation.
Most importantly, the platform uses a tool to improve patient adherence. Tech-enabled blister packs track each pill as it is removed. This allows for real-time intervention if patients miss a dose at the scheduled time.
Where do FDA and EMA stand on unconventional trial designs?
The US Food and Drug Administration (FDA), with its 2019 guidance document about adaptive design clinical trials for drugs and biologics, acknowledges that these types of trial designs can make drug development more efficient and less costly.
FDA confirmed that stakeholders welcome the added flexibility factor of the adaptive clinical trials compared to the more traditional ones, being much more willing to commit to these trials that allow planned designed modifications.
Patients are also more willing to enroll in adaptive trials, as they find that these kinds of studies can increase the probability of being assigned to more effective treatment.
Meanwhile, the recent EU Medicines Agency (EMA) report “EMA Regulatory Science to 2025” has also highlighted the need to foster innovation in clinical trials.
Small eligible patient populations, limited endpoints to demonstrate efficacy and benefit-risk, and the availability of new data sets from digital technologies are all identified as innovation drivers.
All you need to remember about unconventional trial design in a nutshell
- The Covid-19 pandemic stressed further the need for a better patient representation in clinical trials.
- Decreased enrollment boundaries in unconventional trials enhance patient diversity and provide data reflective of the general population.
- In the next few years, we will witness the significant impact of digital technologies in clinical trials. EMA highlights the importance of ensuring digital data quality and validity.
- Despite initial consideration, unconventional trial designs have proven their ability to maintain trial integrity and produce valuable insights. Thus they gain popularity among pharmaceutical companies and investigators.
Are unconventional trial designs here to stay?
What trends, challenges and opportunities emerge in clinical trials? Stay with Lucidquest. There’s more to say!
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Sources:
https://acrpnet.org/2022/04/17/effective-data-analysis-for-nontraditional-study-designs/
https://clarkstonconsulting.com/insights/nonconventional-clinical-trial-design/
https://bmcmedicine.biomedcentral.com/articles/10.1186/s12916-018-1017-7
https://www.clinicaltrialsarena.com/analysis/clinical-trials-in-2022-highlights-for-the-year-ahead/
https://www.fda.gov/media/78495/download
https://pharmaphorum.com/news/janssen-istep-clinical-trial-adherence/