Clinical trials form a vital part of drug development. Throughout the process, physicians test new drugs on carefully selected patient cohorts to establish the safety, efficacy and clinical benefits of these drugs.
Pharmaceutical innovation has never been healthier. Thanks to rapid advances in science and technology, researchers and clinicians are able to harness tools to capture vast amounts of data at near-zero cost, all while gleaning crucial new insights into previously unreachable areas of disease and disease variants.
With a spate of new discoveries in biomedical research, perhaps it’s little wonder that new drug output is at an all-time high. In 2018, the Food and Drug Administration (FDA) — the United States government’s public health regulatory body — approved a total of 61 novel drugs. This was the highest ever number of new drug approvals in a single year, exceeding the 1996 record by over 20 per cent.
There are many facets to the drug development process. Once the pharmaceutical company conducting the research has identified the lead compound through a process of drug discovery, they will then conduct preclinical research on microorganisms. But before the drug can be approved by the necessary regulatory body (such as the FDA), researchers have to prove its safety and efficacy by testing it on human subjects in clinical trials.
Unfortunately, drugs don’t come cheap. According to the Tufts Center for the Study of Drug Development, the cost of developing just one drug — from preclinical testing to market approval — stands at an estimated $2.6bn, with clinical trials being by far the most expensive factor. But why do clinical trials for new drugs cost so much money? And is it possible for the pharmaceutical industry to reduce costs without compromising on safety?
How do clinical trials work?
Clinical trials are research studies involving human volunteers. Most clinical trials are conducted to test novel pharmaceutical treatments and are undertaken in a series of steps called ‘phases’. If a new treatment is successful in one phase, the trial moves onto the next phase. There are three main phases of clinical trials:
Phase I — safety
These are small-scale and typically involve less than 30 healthy volunteers under close medical surveillance. This phase is designed to establish a safe and tolerable dose for a new treatment, ascertain how the treatment should be administered, and learn how it affects the body.
Phase II — efficacy
In this phase, the drug is tested on patients for the first time to determine its effectiveness. Phase II trials — also known as Proof of Principle studies — study the effects of the treatment on the body, as well as how it works for a certain type of illness (e.g. breast cancer). As many as 500 patients may participate in a phase II trial. If the treatment is found to be safe and displays tangible benefits, the trial progresses to phase III.
Phase II — clinical benefit
In this phase, the new drug is tested at a defined dose in large numbers of patients, usually in clinical trials centres. Phase III trials compare the new treatment with existing treatments to identify which is better. To ensure maximal objectivity, these trials are typically double-blinded, meaning neither the patients nor the physicians know which patients are receiving the new drug and which patients are receiving a placebo.
To obtain statistically relevant results, phase III trials can enrol up to 5,000 patients. This phase takes several years to complete and is extremely costly. In fact, a 2018 study in JAMA Internal Medicine estimated that the median cost of phase III trials in the United States is $19 million (£15 million).
Once a drug has been licensed by the country’s regulatory body, phase IV trials may take place. This phase aims to discover more about the side effects of the drug, what the long-term risks and benefits are, and how well the drug works when it is used more widely.
For those who want to participate in clinical trials, eligibility for enrolment depends on what the researchers conducting the trial want to achieve. While some trials require healthy volunteers, for example, others require patients who suffer from a certain illness.
Weighing up the financial cost of clinical trials
When planning a clinical trial, the researchers overseeing the process have to consider factors such as trial design, protocol design, site selection, and trial execution.
Prior to all this, of course, is the question of funding. In the UK, the NHS does not subsidise any clinical trial research. Instead, funding is provided by drug companies, charities, government-funded bodies such as the Medical Research Council (MRC) and the National Institute for Health Research (NIHR), and, on occasion, international organisations.
Once a clinical trial has been given the go-ahead, research and development (R&D) costs can often be eyewatering. A Battelle study published by PhRMA found that the average cost of for one patient in a US-based clinical trial was $36,500 (£28,736). For cancer drugs, the estimated figure stood at $59,500 (£46,843). For infectious diseases, the figure was $16,500 (£12,990).
Meanwhile, another study by Sertkaya et al found that the highest costing indications were pain/anaesthesia, ophthalmology, anti-infective and respiratory. For each of these types of drugs, the corresponding clinical trials cost in excess of $40 million (£31.5 million).
But how are these costs accrued? A clinical trial cost breakdown by Clinical Research IO found that the total spend of a typical clinical trial is meted out as follows:
- 20% on clinical procedures
- 20% on staff and admin
- 14% on site monitoring
- 12% on site retention
- 8% on lab costs
The remaining expenditure goes towards other important considerations such as physicians, site recruiting, source data verification (SDV) and patient recruiting.
How can the cost of clinical trials be alleviated?
According to a Phesi database analysis of over 320,000 clinical trials, 17.2% of Phase II trials and 12.2% of Phase III trials since 2008 have been prematurely terminated due to inadequate planning. Investing time and effort into the planning stage of clinical trials, then, is key.
Though the high prices of running clinical trials are on the rise, pharmaceutical and biotechnology companies are turning to technology to find faster and cheaper ways to plan and execute clinical trials.
Increasingly, clinical teams are conducting studies in accordance with the principles of Adaptive Trial Design (ATD). This strategy evaluates data as the trial progresses, helping researchers to modify any inefficiencies within the process. Similar to agile management strategies, such an iterative approach can make clinical trials more flexible because they make better use of time and money than traditional fixed design.
Adopting a more efficient approach to the electronic data capture (EDC) database build process can also cut costs. With a conventional approach, database build takes around 12 to 16 weeks. With a collaborative approach, on the other hand, the actual build is designed and constructed during system training. In other words, platform experts working closely with research staff to optimise data management workflows.
Finally, leveraging mobile technology for data capture can help researchers collect data more effectively, as well as improve engagement among clinical staff and volunteers. Mobile technology can lead to fewer data errors, more efficient communications, improved patient compliance, faster trials, and greater diversity among participants — all of which add up to substantial cost savings.
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