trends & perspectives in clinical research

goBalto Chromosome

Restricting Regulations

by Craig Morgan

Modern medicine has come a long way since the days of snake oil salesmen. Today, patients can be assured that the medicine they are prescribed has been vetted for safety and efficacy by a long and arduous discovery process guided by governmental regulatory agencies.

Restricting Regulations

The central pillar of this rigorous process for modern drug approval is the human clinical trial. The success of this model has resulted in a proliferation of clinical trials worldwide. Since the International Committee of Medical Journal Editors (ICJME) established trial registration requirements in 2005, there has been a fivefold increase in clinical trial registrations globally. In the United States alone, clinical trial registration has increased tenfold during this same time period.

Against this backdrop the European Union (EU) recorded a concerning 25% decrease in clinical trial applications (CTA) from 2007 to 2011. Why?

Clinical Trials Have Gone Global

One of the issues affecting the number of EU clinical trials is a growing trend towards globalization - with a significant increase recently in trials being conducted in developing countries. The number of countries serving as study locations outside the United States, for example, has more than doubled in the last 10 years, and the proportion of trials undertaken in the United States and Western Europe has reduced significantly.

There are several factors driving this globalization trend – one of the main ones being the spiraling costs of drug development. A 2013 study by the Tufts Center for the Study of Drug Development (CSDD) estimates the average cost to develop and gain market approval for a new drug at a staggering $2.6 billion, up 145% from a similar study conducted in 2003. The costs of conducting trials is by far the largest contributor to these cost increases, and given that the success rate for drugs moving through clinical trials to FDA approval is a mere 10%, the pharmaceutical industry is struggling to sustain profitability. This has resulted in a variety of aggressive actions to minimize clinical study delays and costs, one of which is globalization. Moving trials to developing countries with lower salaries for workers may reduce trial expenditures by up to 60%. Sponsors and CROs have increasingly used global networks to reduce costs and accelerate patient recruitment.

EU Clinical Trials Directive

Another major contributing factor to the decline in CTAs in the EU has been burdensome regulations. The EU Clinical Trials Directive 2001/20/EC was passed by the European Parliament in April of 2001 to facilitate the implementation of good clinical practice (GCP) across the EU in the conduct of clinical trials on medicinal products for human use. The original intention of this directive was to simplify and harmonize the administrative provisions governing regulation of clinical trials. Worthy of note is the fact that this Directive merely provides guidance on clinical trial applications and conduct – each member country must translate this Directive into its own national legislation. Given that each EU member country interpreted this Directive in its own way, each country developed its own unique submission requirements, timelines, classifications, and safety reporting for clinical trials. While Directive 2001/20/EC has facilitated important improvements in the safety and ethical soundness of clinical trials in the EU, it has been widely criticized for serving to increase both the time and costs of conducting clinical trials. Since the passage of EU Clinical Trials Directive 2001/20/EC, the following has occurred:

  • Staffing requirements for the clinical trial authorization process for sponsors has doubled.
  • Insurance fees have increased by 800 percent for industry sponsors.
  • There has been a 98 percent increase in administrative costs for non-commercial sponsors.
  • Delays for launching a clinical trial increased by 90 percent to 152 days.

Given these cost increases inherent in running clinical trials in the EU, many sponsors have simply chosen to conduct their trials elsewhere.

New EU Regulations Harmonize Clinical Trial Requirements

As one potential solution to this problem, efforts are being made to harmonize clinical trial standards within and between member countries. In 2014, the European Commission adopted a new regulation EU Regulation number 536/2014, with the intention to simplify the submission of an application dossier for trial authorization and harmonize the procedures for conducting clinical trials across member countries. This new regulation is binding across all member states, and is expected to go into effect in 2018.

There are several important simplifications inherent in this Regulation that are expected to make it a major improvement over the Clinical Trials Directive currently in use:

  • A single portal for the submission of the clinical trial applications, no matter how many countries are involved
  • A single decision on the CTA submitted through the EU portal, as opposed to separate decisions from each member state
  • A national level body will review the documents as per the national applicable law, but with only one contact point and one fee per country.
  • Review timelines have been established - a total maximum time of 106 days is allowed for the initial submission, although advanced therapy trials can take up to 156 days.
  • Regulation of clinical trials throughout the member states is harmonized
  • Simplified reporting procedures
  • Increased transparency of clinical trial results

The first simplification listed above is perhaps the most significant, as it effectively reduces what might have been a total of 28 required application dossier submissions (one for each member state) down to just one.

Cloud-Based Solutions

The trend towards globalization of clinical trials has led sponsors and CROs to adopt cloud-based solutions, such as study startup (SSU) solutions that serve to expedite the startup process for multi-site studies across countries with disparate requirements. These solutions help to simplify the complicated site activation activities encountered by global multi-site studies with standardized country-specific workflows and streamlined document management. Cloud-based SSU solutions have the potential to help realize what the EU Clinical Trial Directive failed to accomplish – improve both the ease and efficiency of the clinical trial approval process. Additionally, goBalto recently announced that their Activate SSU software is compliant with the new EU Regulation 536/2014, and will thus allow users to seamlessly transition from the current regulatory framework once this new regulation goes into effect.


In response to the decline in clinical trials across the European Union, the European Commission has adopted EU Regulation number 536/2014. Hopes are high that this new regulation will serve to turn the situation around and attract more clinical trials to the EU. The globalization of clinical trials will likely continue, however, and even the harmonized procedures in this new regulation may not be enough to completely reverse this trend. Still, efforts by the EU and other governmental agencies around the world to harmonize and simplify regulations towards the goal of expediting clinical trials are important and should continue. While protecting the safety of patients and assuring the efficacy of medications should remain paramount, excessive and burdensome regulations only serve to slow the release of valuable, life-saving therapies to patients.

Article published in International Clinical Trials, October 2017

Recent Posts