Imaging, this non-invasive tool of clinical research, bears a number of benefits for the development of medical science in general and progression of clinical studies in particular. This is the reason why there is a strong and growing trend of deeply incorporating novel imaging technologies into clinical trials, making them a constituent part of biotech, pharma, and medical device development processes.
This is how clinical trials can benefit from incorporating imaging:
- Reduced drug development time and accelerated regulatory approval.
- Access to tissues that are inaccessible for sampling through biopsy (like lesions in cancer patients).
- Reduction of the overall study budget in certain cases of molecular-level disease scenarios and in precision medicine (prescribing targeted therapy) through screening and stratification of those patients who are more likely to respond to the drug being tested.
However, along with benefits, there are a number of obstacles that speed down the process of clinical imaging’s more intensive integration into the medical research process. And they also will be presented in this article along with some solutions to overcome or reduce their hurdling effect.
What is Clinical Imaging Currently Used for?
The following are the major directions medical imaging is used in clinical research today:
- To accelerate clinical trials using imaging as a primary, quantitative, and surrogate biomarker. Using imaging as an endpoint for primary study (with a due amount of forethought) allows for bringing new drugs to market sooner for such unmet needs as orphan diseases. This is a valuable opportunity imaging provides given the drug development’s increasing cost and timelines. Actually, today, in a lot of clinical studies “centralized” imaging data is used as a primary endpoint.
- To enhance clinical trials of early-phase which have less logistical challenges but are more dynamic, involving more scientific research than trials of later phases and requiring study structuring and more image-relying protocol.
- To ease regulatory approval in the late phase of trials, with the focus of imaging shifting toward streamlining of operation workflow for efficient trial management.
A Retrospective Journey into Medical Imaging History
In 1997, Imaging modalities were allowed to be used by the FDA Modernization Act (FDAMA) in clinical trials as a tool for development of both drugs and medical devices. According to this document, data that were gathered through imaging modalities could be included in the research paperwork generated for regulatory submission.
In 2004, with its Clinical Research Initiative (CPI), FDA allowed the use of modern technological and scientific tools (such as imaging) to improve the accuracy of results during the clinical study and predict the efficacy, safety, and manufacturability of medical products being developed.
In 2011, the FDA released the Clinical Trial Imaging Endpoint Process Standards document containing standards to be used by sponsors to ensure that the collected imaging data meet the following requirements:
- the imaging data should comply with the trial standards and protocols,
- the imaging data should provide a variable record of the process of imaging,
- the imaging data quality should be maintained within as well as among clinical sites.
These regulations resulted the growth of the market of core laboratory imaging services and enhanced the incorporation of imaging into clinical research. Over time, this resulted in $773.4 million worth global imaging market in 2016, with an estimated CAGR of 6–8% till 2020. Over 70% of the clinical trial imaging market is shared among top 5 medical imaging service providers.
Challenges to Integrating Imaging into Clinical Research
Integration of imaging as an instrument of clinical medical research on a worldwide scale presents certain challenges like:
- Availability of advanced imaging technologies – not all medical facilities (depending on geography) have the required equipment, which makes site selection for multicenter and multinational studies complicated.
- Availability of high-speed internet connection and corresponding software – not all sites have a reliable network connection and/or software to document and upload all changes and modifications in compliance with 21 CFR Part 11. These factors strongly impact timeline and quality of the research.
- Considerable cost added to medical research with the introduction of imaging and creation of core laboratories.
- Privacy concerns in terms of DDoS attacks on cloud computing services on connected imaging systems.
- Reluctance in adopting imaging as a biomarker – sometimes this method is perceived as qualitative and imprecise to rely on when making conclusions on drug efficacy.
- Intra- and inter-reader variability caused by differences in reading and/or evaluation/assessment criteria used by different physicians.
- Complexity of protocols related to study set-up and other conditions of using imaging as a clinical trial primary endpoint which can cause delays in the timeline.
However, the fact is that despite all these issues and challenges, the medical imaging industry enjoys increased interest and investment.
Core Lab as the Best Place for Centralized Compilation and Reading of Clinical Images
Data collection and further assessment in a centralized imaging core laboratory or CRO prevent biases in the reading of the collected images. In order to provide credibility and consistency of imaging data in compliance with the FDA requirements, these activities should be performed in blinded manner by the endpoint assessment committee. There are also a number of other requirements to be observed like data to be captured in digitized form only (and not as image films), trial-specific standards to be well-defined and reliable, etc.
However, the cost of core laboratories is fairly high due to the following factors:
- Use of proprietary customized software for image uploading, analysis, data processing, de-identification, and storage.
- Staff costs, with about 50–60% of them being attributed to radiologists alone, whereas working at a typical clinical trial are also a medical imaging technologist, a project manager, biostatistician, technical services manager, clinical IT specialist, imaging physicist/ scientist, and logistics staff responsible for study site management, site set-up, and image transfer (on mediums like a CD or DVD) from technologically less saves sites.
- Administrative costs like those for facility maintenance and rent.
Solutions to Ease the Use of Imaging in Clinical Research
Data collection and image analysis are extremely time- and money-consuming, bearing also high risk level of delays in clinical trial timeline caused by human errors. Certain specially developed technical solutions and regulations are being introduced to decrease the time physicians spend analyzing images as well as the probability of errors they make when assessing images.
As costly as it is, in the long run, clinical imaging can save sponsors a lot of money by helping evaluate drug and device efficacy on earlier stages of research, which allows to direct investments towards effective therapies, sorting out the ineffective ones early on. The other way clinical imaging is beneficial for CROs and medical research is that it helps identify patients who are most likely to benefit from the drug.