While necessary to describe changes to the protocol that significantly affects patient safety, the scope of the investigation, or the scientific quality of the study; the incremental costs of amendments and the associated study delays can be enormous. Considering internal FTE time dedicated to implementing each protocol amendment, costs or fees associated with protocol language translation, and time and costs associated with resubmission to the local authority as well as increases in investigative site fees and contract change orders with vendors unnecessary amendments should be avoided at all costs.
Why do they occur?
The most common causes of amendments include regulatory agency requests, new safety or dose-related information about the study drug, new standards of care, competitive pressures, protocol design inconsistencies and flaws, and patient recruitment difficulties.
A recent study by Tufts CSDD indicate that one-third of all amendments are avoidable.
Undetected design flaws, inconsistencies, or errors in the protocol, and difficulties recruiting subjects are causes that sponsors might have anticipated and avoided with better upfront protocol planning and review. This is in line with the fact that a high percentage of amendments occur before first patient first dose.
Avoiding the unnecessary
To avoid delays and expenses, how can study sponsors minimize the number of protocols through better initial study design and recruitment?
Faced with time and budget pressures, sponsors often need to move forward while regulatory decisions are pending or new standards of care evolve. However, sponsors can minimize the number of avoidable protocol amendments by better protocol design planning.
Sponsors also need to come to a more informed decision-making. They need to adapt their strategies to evaluate changes of standard of care, obtain solid and meaningful feasibility data and scientific advice from KOLs and in-depths understanding of the opinions of the regulatory authorities and other stakeholders such as the health insurance funds in the different regions where the study is conducted.