How to cut the negative impact of protocol amendments in clinical trials

Written by Ian Macholl

Social distancing laws in response to the COVID-19 pandemic forced dramatic changes to procedures for the collection, monitoring, review and analysis of clinical data in trials. Regulators have responded with an appropriate degree of flexibility but some CROs initially struggled to manage the impact on clinical trials.

Protocol amendments are more common in clinical trials than you might think. A 2017 article by the Tufts Center for the Study of Drug Development (CSDD) found 59% of clinical trials have at least one protocol amendment (PA). The Phase II studies reviewed in the Tufts research had on average 2.7 amendments per protocol while the rate was higher for Phase III studies at 3.6 amendments per protocol. Our experience is that 79% of clinical trials have at least one protocol amendment.

Why should this matter? Protocol amendments have a major impact on CRF design, which typically lead to delays and system downtime for CRF updates, and ultimately increased costs for sponsors. It’s important also to highlight the frustration experienced at sites due to their inability to enter data during system downtime, which leads to backlogs in data entry.

Protocol amendments surveyed by the Tufts research cost on average $141,000 each for Phase II trials, while Phase III PAs were $535,000 per amendment. More significantly, the opportunity cost from delayed trials are far higher. Studies with protocol amendments take on average 6 months longer from protocol approval to last patient first visit than others. Furthermore, they were 90 days longer from last patient last visit to database lock, according to the Tufts research.

Whilst some protocol amendments can be avoided, the majority are required in response to external, unforeseeable changes such as new safety information.

Clearly, it is important to work with a CRO that is able to minimise the impact of protocol amendments on trial timelines. Cmed is a CRO that specialises in leveraging technology and experience to optimize efficiency, particularly by being more agile and flexible than other CROs in multiple ways:

  • We have flexible processes that can adapt to change easily. Many of our clients come to us with bad experiences of working with large CROs with rigid procedures embedded into their large internal structures.
  • We offer protocol development services, using our expertise to set the original protocol with the most flexibility while maintaining safety standards and a focus on delivering the right endpoints for your study.
  • We plan database design carefully at the outset of your trial. This takes specialist skill but enables changes to be made mid-study much more easily.
  • Our 140-strong data teams are highly experienced. There is practically no problem that we haven’t come across previously or that we can’t handle.
Cmed team icon

Average experience

Lead Data Managers: 12+ years

Biostatisticians: 15+ years

Senior Statistical Programmers: 10+ years

  • We use latest technologies including encapsia which accommodates changes to the CRF design much more easily than popular systems like Rave. Most importantly, using encapsia there is no system downtime during database upgrades, which dramatically reduces the impact on site experience by reducing or eliminating the data entry backlog.
  • We communicate and work in partnership with sponsors and sites to solve problems through teamworking. That’s why our 2019 client survey rated us as 4.7/5 for communication
Cmed's 2019 client survey results
Cmed's 2019 client survey results
  • We maintain the team, we don’t swap and change. We stay familiar with the study so we can respond more quickly to unexpected changes. The team you meet before you work with us is the same team you work with after your project commences.

When planning a clinical trial it’s common for sponsors to overlook or underestimate the possibility of protocol amendments. The COVID-19 outbreak has shown the inflexibilities of much of the clinical trials industry but Cmed has remained focused on being agile and flexible to minimize the impact of protocol amendments on your trial.

For a no obligation discussion with one of our clinical trial experts about how we can support your next trial please contact us.