A steady and efficient influx of novel medical solutions is critical for meeting society’s current and future medical needs. The clinical research industry is responsible for the delivery of these solutions to society by systematically evaluating their safety and efficacy in so-called clinical trials. But what do clinical trials exactly entail and why are they so important to patients, drugmakers, regulators, and society at large?

This article was adapted from Chapter 1 of the Triall whitepaper (which you can download using this link). Triall’s mission is to enable a future of smarter, safer and more-efficient clinical trials by introducing a blockchain-enabled ecosystem for clinical trial stakeholders.

The era of modern medicine

With the introduction of organic chemistry and our ability to isolate, examine and systematically measure the effects of chemically active ingredients in the body, society has transitioned into the era of modern medicine. Since then, the world has witnessed the introduction of increasingly sophisticated medical technologies and approaches that have realized the eradication of previously ‘unbeatable’ infectious diseases, halted their epidemics, and raised global life expectancies and well-being to unprecedented levels.

Shifting from one unmet need to another

While these achievements are impressive, coming up with a solution to a medical problem often means shifting from one unmet medical need to another. Due to increasing life expectancies, for instance, health systems throughout the world now struggle with increasing incidence rates of diseases related to old age. In addition, converting diseases that were once untreatable and life-threatening into chronic conditions requires society to come up with innovative treatment approaches.

Clinical trials: delivering medical solutions to society

Novel medical solutions take the form of new and improved treatment approaches and technologies, such as drugs, diagnostics, vaccines or medical devices. To ensure their safety and efficacy in the target patient population, candidate medical innovations are subjected to a carefully regulated process of systematic evaluation: clinical trials.

Facts and Figures: over half of the global pharmaceutical R&D budget (totaling US$ 172 billion in 2018) is currently spent on clinical trials. The market for clinical trials is dominated by European and North-American organizations, and roughly 80% of all research subjects enrolled in trials origin from these regions.

Clinical trials involve many different specialist stakeholders

A clinical trial is initiated by a sponsor: a pharma, biotech or medical devices company, academic institution, or governmental body that aims to introduce a new treatment to society. Before starting a trial, the sponsor often conducts a partner selection process to outsource some or all of its trial-related tasks and duties to one or more specialized service providers, known as contract research organizations (CROs). These CROs can be contracted for tasks such as data monitoring, manufacturing of the investigational product, regulatory affairs, or overall project management for the trial.

The clinical trial can then be initiated, but only after explicit formal approval from an independent ethics committee (EC) and the national competent authority (CA) in the country where the trial is to be conducted (multiple committees and authorities in the case of a multi-country trial).

After approval, the bulk of the actual trial activities take place at research sites, either (academic) hospitals or dedicated clinical research centers, and consists of patient visits and treatment administration. Throughout a trial, all of these stakeholders need to interact and collaborate in a broad range of trial-related activities, such as study approval, site monitoring, data management, safety reporting, regulatory filing, medical writing, and research dissemination.

Different phases of clinical trials: clinical development is divided into several consecutive phases, starting with Phase 1 clinical trials that are aimed at examining the product’s safety and dosing levels in around 20 to 100 healthy human volunteers. Phase 2 trials involve up to several hundred patients and are aimed at establishing ‘Proof of Concept’ for the medicinal candidate. In other words, these trials evaluate a product’s efficacy and assess its side effects. Phase 3 clinical trials gather evidence on efficacy and side effects to an even greater extent, including 300–3000 patients and taking several years to complete. Ultimately, these trials aim to investigate whether the novel treatment offers an added benefit to the patient and society compared to existing approaches. After Phase 3, the evidence gathered during phase 1–3 is formally reviewed by the applicable market regulator, such as the US Food and Drug Administration (FDA) or the European Medicines Agency (EMA), who can authorize the product for market introduction. To this end, a ‘registration dossier’ is submitted that should contain all gathered data on quality, safety, and efficacy of the candidate product for its intended use.

The rise of clinical trial regulations

The evaluation of candidate medicinal products in human subjects has become highly regulated as a consequence of several catastrophic events in the past. For instance, the Nuremberg Code of 1948, advocating voluntary participation and informed consent for participants in medical research, can be seen as a direct result of involuntary medical experiments conducted during World War II.

Similarly, the obligation to obtain approval from the FDA for marketing a new drug was only mandated after the ‘thalidomide tragedy’ of the late 1950s, in which the drug thalidomide was found to cause severe fetal deformities only after it had already been introduced in 46 different countries. The faulty market introduction of thalidomide for treating morning sickness in pregnant women resulted in an estimated 10,000 babies being born with severe deformations.

In 1964, the Declaration of Helsinki was established by the World Medical Association, forming the basis for good and ethical research conduct. The aim of this declaration is to protect the rights of human subjects involved in medical research by providing a set of ethical principles mainly targeted at physicians.

Good Clinical Practice

Nowadays, clinical trials are conducted in compliance with Good Clinical Practice (GCP), ‘an international ethical and scientific quality standard for designing, conducting, recording and reporting trials that involve the participation of human subjects. Compliance with this standard provides public assurance that the rights, safety, and well-being of trial subjects are protected, consistent with the principles that have their origin in the Declaration of Helsinki, and that the clinical trial data are credible’ (International Conference on Harmonization, 2016).

“Nowadays, clinical trials are conducted in compliance with Good Clinical Practice (GCP), an international ethical and scientific quality standard for designing, conducting, recording and reporting trials that involve the participation of human subjects.”

Complex, lengthy and resource-inefficient: issues with clinical trials Strikingly, despite today’s advancements in science and technology, the speed, costs, and success rates of clinical trials have not improved over the years and in some instances operating conditions have gotten worse. Ongoing research has shown that the overall cost of drug development continues to rise with an average of 9% each year. Moreover, development cycle times have become longer and less predictable, indicated by the increasing incidence of changes and delays. This has resulted in a situation where success rates for new candidate medicinal products in clinical development are at an all-time low, with only 11% ultimately making it to the market.

Aiming for a future of smarter, safer and more-efficient clinical trials

At Triall, we are passionate about tackling some of the persisting issues that hamper the introduction of novel medical solutions to society. We strongly believe blockchain technology can be used to address various suboptimal processes and activities that frustrate today’s clinical trials. As we see this as a shared effort, we have brought together a consortium of experts and opinion leaders in clinical development, clinical trial IT and blockchain technology. Together, we are developing a set of blockchain-enabled applications and APIs that are all geared towards enabling a future of smarter, safer and more-efficient clinical trials.

More info on our first application can be found here.