Why Are We Failing to Implement Imaging Studies with Radiolabelled New Molecular Entities in Early Oncology Drug Development?

Table 2

Sequential stages of activities, their timelines, potential causes for delays, and recommendations to reduce delays in PET biodistribution studies.

Activities	Approx. time (months)	Potential causes for delays	Comments and recommendations for improvement in timelines
Stage I (all activities can be done simultaneously): time 1-2 months
Initial study discussion formulation of an outline research plan	2 months	Prevarication, and absence of key decision makers	Clear communication and clear goal setting by the respective team leaders
Confidentiality agreements completion	1-2 months	Legal issues	Preexistence of a master services agreements
Formation of study teams with clear definition of roles and responsibilities	1 month	Organisational issues; Availability of experienced staff and agreement	Ensure inclusion of key staff, chemists, regulatory, clinical, biologists
Contract agreements	1-2 months	Disagreements on pricing and intellectual property rights	Early finance and legal involvement. Work with contract-based imaging services providers
Stage II  (all activities can be done simultaneously): time 4–7 months
Radiochemistry feasibility and production of radiolabelled NME (non-GMP or GMP); Implementation of GMP radiochemistry (RC) and its validation; Preclinical dosimetry study; Animal toxicology studies	4–7 months	Radiochemical method development issues; Issues with procurement of precursor (GMP or non-GMP); Problems transferring from non-GMP to GMP settings	Selection of PET centre with good track record of developing and implementing radiopharmaceuticals for clinical use and management of drug maker expectations; Preferred approved suppliers; Duplication of equipment for straightforward transfer of methods, development of cassette based chemistry, good communication, and regular interactions; Agreement of clear milestones and associated timelines for “Go-No Go” decisions
Stage III (all activities can be done simultaneously): time 3–6 months
Preparation of IMPD dossier for submission to MHRA	1 month	Subject to delays in GMP implementation	Experienced personnel to complete CMC section
Identification of clinical collaborators; Initiation of contracts with hospital	3 months	Identification and selection of appropriate clinicians; Realistic assessment of recruiting potential	Initiate early in Stage III as can cause significant delays; Preferred clinicians, imaging centre-linked clinical units
Development of research study protocol	2 months	Internal hierarchical and regulatory approval
Preparation and submission of regulatory submission to the REC, MHRA, and ARSAC and to hospital R and D	2 months	CMC section completion due to RC implementation delays; Delays in getting a date for an REC meeting	Done via the common IRAS However, MHRA and ARSAC require additional information to that provided by IRAS
Obtaining regulatory approvals and study initiation	2-3 months	Delays if there are queries or need for modifications; Variable calibre of ethics committee to review such studies	Hospital R and D approval not time-bound; Submission to or designation of ethics committees to review such studies