Developing new drugs and treatments is crucial for advancements in medical options for those with illness, disease, and injuries, as well as for proactive, personalised healthcare. Decades ago, medical technology and medications could not provide the quality of life available to ailing patients today. Researchers are always in search of ways to improve medical outcomes, and clinical trials are a cornerstone of these advancements. For example, in recent years, clinical trials found CBD to be an effective treatment for two severe rare forms of epilepsy1 , ultimately leading to government approvalsof pharmaceutical-grade CBD.2
However, clinical trials are expensive and time-consuming. On average, it takes six to seven years to complete clinical trails and about $2.6 billion.3 They can also be a burden for participants. When they fail, it is often a result of failure to demonstrate efficacy and safety, low participation, patient drop-out, and lack of funding.4 A drug that is effective and safe can fail to demonstrate efficacy and safety through poor trial design, poor trial execution, or insufficient data due to inadequate enrollment.
Funding issues often occur when mistakes take place. Common mistakes in clinical trials include overestimating participation, designing a trial that is too complex, attempting to collect an excessive amount of data, issue with following patients, randomization errors, drawing incorrect conclusions unsupported by the data, and making mistakes in statistical analysis and programming.5 Mistakes can prolong the trial, which inevitably necessitates more money than was originally calculated.
Understanding clinical trial best practices can help drug developers avoid pitfalls before they arise. Each year, hundreds of thousands of clinical trials attempt to find novel ways to treat diseases,6 but few lead to approval. In 2019, the FDA only approved 48 new medications.7
ICON rigorously adheres to clinical trial best practices devised through extensive experience in the field. As a result, ICON is frequently able to move through trials more quickly and efficiently. Below is information detailing some of our best practices to better comprehend the process of what makes a clinical trial successful.
Trial enrollment and site acquisition
Before launching a trial, it is important to understand the correct foundational actions that will set a trial up for success before it even begins, including trial enrollment.
Slow enrollment is a common challenge, stemming from a variety of factors, including a feasible recruitment plan, providing information in a way that potential participants can understand, and ensuring participants have easy access through appropriate site selection or trial decentralisation.
Aside from its relationship to enrollment, the site selection should consider everything the trial will require. For example, many trials require multiple sites, such as specialised clinics, private practices, and hospitals. Some trials require nonstandard equipment. Trial management should secure sites as soon as possible to help satisfy the trial expectations for location, equipment, and space.
Furthermore, sponsors can help to resolve the issue of getting easy-to-understand information out to potential trial participants by providing pamphlets that clearly explains the in’s and out’s of the trial, the expectations of participants, and what participants will receive or gain from the study. During the study, relevant trial staff should explain the standards of procedure to participants, whether or not they seem self-explanatory. This will avoid participants’ confusion or frustration and keep the process running smoothly
Choosing the right site is of utmost important to the success of a study, as it can impact both enrollment and retention of trial participants. Common clinical trials sites include clinics, hospitals, and universities.
The process of locking down trial sites involves much more than finding sites with space that agree to do it. Trial facilities must have the capacity to conduct the trial in other ways. The site should have processes in place that can effectively manage the trial participants and equipment. If the trial involves the use of a specific device or piece of equipment the facility does not have, another trial site must be found, or it must be brought in.
Additionally, choosing trial sites involve finding the right site for each study. They should be based on relevant experience of the site’s healthcare professionals, location that suits the trial participants, disease prevalence in the location of the site, the technology available at the site, and access to a pharmacy capable of meeting the study’s requirements.
Before the clinical trial starts, trial management should conduct an initial risk assessment to prepare for potential issues. It is important to identify and categorise risks ahead of time to help avoid them altogether or at least have a plan for mitigating them. This encompasses issues that could arise with the trial and its participants and also between the sponsor and the CRO, the trial sites, and vendors. In the case of an issue, recognising the best way and with whom to communicate can prevent confusion, avoid delays, and speed up the process of solving problems that may arise.
ICON can help with this. Our safety surveillance team performs analysis of signals or trends that may be evident in a dataset as well as monitoring and review of any adverse events of special interest. ICON can generate meaningful outputs and visualisations using Spotfire® to facilitate the review of safety data and identification of safety signals.
Where signal validation and assessment are required, we can support review of prior awareness, strength of the evidence, analysis of sub-population at higher risk and clinical relevance of the signal. If need be, ICON assesses other relevant data sources such as regulatory databases, claims databases or scientific literature.
For more information, check out how ICON prioritizes patient safety.
While clinical trials are testing the safety and efficacy of therapeutics, it’s not necessarily an “experiment” –by the time drugs get to first-in-human trials, they’ve already been through intensive study and analysis. Regardless, the safety of the trial participants must be a priority at all times.8 The trial should be designed to appropriately monitor and protect participants. Safety is also an issue when considering the clinical trial results. Trial management must accurately record trial data to ensure proper drug development. Failure to record trial data can lead to the use of false information when developing a drug or treatment and can have dire consequences, such as the approval of unsafe drugs for public use.
Clinical trials must follow legal and regulatory requirements, which are put in place for safety reasons. ICON can help sponsors plan for and meet regulatory requirements with a strategic approach to global regulatory affairs, submissions and interactions with regulatory agencies, and quality and compliance support.
Clinical safety in data management is also a concern in the digital age. Patient privacy is a top concern. Trial personnel must be able to safely report all data and agree to comply with the proper reporting requirements, which are established to protect participants’ data.
Clear research guidance documents and properly trained staff
Personnel running clinical trials must have access to any relevant guidance documents specific to the trial. The documents must be clear to allow the trial personnel to understand how to accurately conduct the trial and record data. Furthermore, staff review those documents regularly, as they often contain complex information. Without clear documents and easy access to those documents, a clinical trial can easily experience delays resulting from unnecessary mistakes. These documents include, but are not limited to, the investigator’s brochure of relevant and current scientific information, normal value ranges associated with all aspects of the study, instructions for how to handle any materials related to the trial, procedures for decoding blinded trials, and a master randomisation list.9
A successful clinical relies on the staff conducting the trial as much as it relies on a well-designed trial. Inadequate staff training can significantly impact the quality of the research results. Requirements in terms of personnel training will depend on the nature of the trial. Some necessitate staff members who specialise in specific devices or equipment to properly conduct the research. The trial management should arrange this beforehand to avoid delays while the trial is ongoing. Trial personnel should also maintain awareness of quality-control procedures, data collection methods, safety, and privacy, all of which are crucial for trial success.
ICON provides assistance in helping sponsors find the right personnel for each study, ensuring the staff is qualified and experienced. We also guarantee the staff receives the training they need to successfully perform the trial, including preparing them for the research policy changing mid-trial depending on early results and situational issues. Early awareness of potential changes will facilitate a smoother process in making adjustments later on.
A successful clinical trial requires establishing a quality assurance procedure. This involves gathering clean data and recording it accurately. Having enough participants and finding sites to host the trial mean nothing if the data ends up inaccurate at some point in the process of the trial. For example, errors commonly occur as the result of mistakes in recording data and misinterpretation of the trial documents.8
To help avoid these kinds of mistakes, trial management should establish a specific protocol to ensure trial quality beforehand so all trial personnel are on the same page and grasp what to do. The protocol often includes re-checking the data, evaluating the credibility of outlying data points, and conscientiously record query identification and resolution throughout the length of the trial.
Trial management can ensure quality by reviewing the data early in the trial and throughout the trial. For routine checks on data quality, trial management should implement ways to track it as it comes in. If data quality issues are detected early enough, it’s quicker and easier to correct them. This covers things like on-site issue correction and retraining trial personnel.
In addition to hosting numerous sponsor visits and audits each year, ICON’s quality assurance department conducts rigorous internal audits to ensure that our commitment to one quality standard and process is achieved.
ICON Central Laboratories hosts over 100 sponsor audits and visits each year. Our Quality Assurance staff will gladly work with clients and prospective clients to plan and schedule an audit. Following each audit our Quality Assurance Department carefully reviews the audit report and continually refines our operations according to client expectations and requirements.
In addition to sponsoring client audits, ICON Central Laboratories’ Quality Assurance Department conducts internal processes audits. Key suppliers are also audited to ensure that these facilities meet our own standards and those of the appropriate regulatory authorities to which they are accountable.
Furthermore, ICONIK, our proprietary technology platform, collects real-time data during the trial process enabling better decision making and the successful implementation of clinical trial strategies.
This also enables us to review your data holistically, and identify site trends or potential risks earlier in the trial. We combine data management expertise, best practice processes with ICONIK to drive success in studies.
The requirements for performing efficient and effective clinical trials are rigorous and complex. Sponsors often choose to work with CROs for clinical trials precisely for this reason. ICON is recognised as a world leading CRO with a global team of experts with extensive experience in a broad range of therapeutic areas. Our mission is to help sponsors accelerate the development of drugs and devices that save lives and improve quality of life, and it all starts with successful clinical trials.
References
1. https://link.springer.com/article/10.1007/s40261-021-01003-y
3. http://phrma-docs.phrma.org/sites/default/files/pdf/rd_brochure_022307.pdf
4. https://link.springer.com/chapter/10.1007/978-3-319-53877-8_43
5. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6092479/#:~:text
6. https://clinicaltrials.gov/ct2/resources/trends#LocationsOfRegisteredStudies
8. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3834937/
9. https://ichgcp.net/8-essential-documents-for-the-conduct-of-a-clinical-trial
Jess Lakritz 