90% of Clinical Trials fail. Even after all the investment in time and resources, only 1 out of 10 clinical projects passes testing and regulatory approval. According to Dr. Duxin Sun, a professor of Pharmaceutical Sciences at the University of Michigan, developing one successful drug through clinical projects takes around 10 to 15 years and $1 billion to complete.
Clinical Operations may fail due to drug performance, clinical operations management, or legalities. Failure may emerge from avoidable mistakes like poor planning and management and misunderstanding biological processes or drug development. However, some culprits for the failure of clinical projects may arise from unpreventable events.
As stated in a review written by David. B. Fogel, “Factors Associated With Clinical Trials That Fail and Opportunities for Improving The Likelihood of Success: A Review” (2018), there are many chances that failures can arise from clinical trials for new drugs or new medical devices. Failures in such trials can come from lack of efficacy, lack of funding, safety issues, and even nonobservance of FDA regulations or government policies.
Most clinical trials fail because of the inability to exhibit efficacy. According to Fogel (2018), the reasons why potentially efficient drugs fail in a clinical operation can be pointed out as flawed study design, inappropriate statistical endpoint, or underwhelming clinical trial in terms of sample size. Unfortunately, these shortcomings can only be seen later in the clinical projects; Phase 3 to be exact.
In a paper published by Thomas Hwang, Daniel Carpenter, & Julie Lauffenburger, “Failure of Investigational Drugs in Late-Stage Clinical Development and Publication of Trial Results” (2016), phase 3 in trials can provide the highest percentage of success in experimental treatment. However, even though remarkable investments on the side of participants, researchers, and sponsors have taken place, many experimental treatments still fail at this point.
Hwang, et. al (2016), also added that drugs in their development stages are on their superlatives. However, in these phases, breakthroughs are rare. However, as also stated in the aforementioned paper, drugs that didn’t show signs of efficacy can still be significant for future purposes and evaluation.
17% of failures in Phase 3 of clinical projects are linked to safety. Although safety is of the utmost importance in a trial not only for the researchers but also for the participants as well, failures in safety are still apparent, especially in clinical studies that have bigger sample sizes or populations. Hwang, et. al (2016) states that safety issues can only be evident in Phase 3 or even in Phase 4 of a clinical trial.
Sometimes, drugs can even be withdrawn even after Phase 4 or the “post-market” stage. This system endorsed by the FDA is called “Pharmacovigilance”. Patients or consumers are encouraged to report any adverse or side effects they are experiencing to collect data and decide whether drugs that are fresh from the clinical trials should be withdrawn from the public or not.
According to Mark Crowther, in his published article “Phase 4 Research: What Happens When The Rubber Meets The Road” (2013), states that phase 4 is required to examine a drug’s performance overtime to anticipate any toxicity or any abnormal events that didn’t take place in previous phases. Furthermore, he added that “Pharmacovigilance” or post-market surveillance remains an integral tool to detect infrequent toxicity. As an additional explanation, he added that the reason Pharmacovigilance is important is that detecting all clinically relevant side effects in sufficient sample size is unfeasible.
Crowther (2013) also gave examples of drugs that were withdrawn from the public due to toxicity detected via Pharmacovigilance. One is Cevastatin, a cholesterol-lowering agent, that was pulled out from the public due to fatalities. Failures in safety can still provide the public information as to what drugs should be avoided and be reported to the FDA.
Inexperienced and unmotivated staff are two components of a disastrous clinical operations department. According to Artem Andrianov Ph. D, in his published article “7 Reasons Why Clinical Trials Fail”, he said that the top 2 contributors to organizational failure in clinical projects are unskilled clinical project managers and unproductive clinical operations management.
Clinical Project Managers
Clinical project managers are expected to be experienced, excellent, and expert clinical staff. The problem arises when the clinical project manager has little to no experience. This problem can be possible if a former associate fresh from a clinical project manager training or a newly moved up CRA (Clinical Research Associate) is being placed to take the role of a Clinical Operations Manager. The promotion isn’t the problem, but because of the evident lack of experience, a new CPM or a Biotech can set unrealistic timelines, discord between stakeholders and the staff in decision-making, and unproductive group due to lack of managerial experience.
Negligence of Legalities
According to Chris Plaford, in his published article “Why Do Most Clinical Trials Fail?” (2015), one frequent problem why there is a delay or failure in clinical operations management is the inability to prepare and complete the required criteria set by the FDA. Companies or Clinical organizations that don’t prioritize completing such requisites imposed by the FDA can jeopardize their chances for approval or can face complete rejection of the drug itself.
Hwang et. al (2016), said that many trials are underfunded. Because of this unfortunate state, many trials may not have the ability to generate beneficial outcomes. 22% of the failures in phase 3 of clinical operations are related to cost issues. The cost of bringing a drug to a market varies. However, some Clinical Operations reported that they have spent $2.5 billion to complete the whole testing with desired accuracy, efficacy, and results. This could mean that underfunded clinical projects can only produce underwhelming, insignificant, and inaccurate results concerning predetermined levels from the planning phase.
Anything can go wrong, but that doesn’t mean success is impossible. This also applies to Clinical Trials and Clinical Operations Management. Nothing can ever go 100% according to the plan, but with clinical operations consulting, clinical operations solutions, and clinical operations expertise, the odds will be in the researcher's favor.