How many times have you been in a hospital? How many times have you been in an oncology department full of people under treatment? How many of us have witnessed someone close being under these treatments?
Oncology studies stand for improvement and in some cases total cure of some types of cancer. The rational design of targeted drugs triggers changes in the design of these studies. Patient populations are more precisely defined and pose a challenge to the efficient inclusion of study patients.
Objectives shift from the definition of a maximum tolerated dose to the evaluation of a recommended phase 2 dose. Other challenges related to the efficacy and safety profile of novel targeted anti-cancer drugs call for changes in designing first-in-human studies, such as definitions of biological doses, a collection of fresh tumor tissue for surrogate marker analyses, and the management of infusion-related reactions with monoclonal antibodies. People who are participating are already patients in different stages of this disease. This makes it highly important and essential that oncology studies must be set up correctly in details, right from the beginning, not just for the benefit of the pharmaceutical company but also everyone involved in this procedure (laboratories, patients, distribution centers, medical clinics, warehouses etc.). Blood samples are precious as they carry a lot of information! This means that when project management and clinical trials teams are discussing the set up of a study is highly important that scientists from both sides are present to discuss and decide all those scientific details that these teams are not obliged to be aware of, but is requested to participate in.
Type of tubes for the blood draw, type of tubes for isolation, reagents, allocation of cells in aliquots, troubleshooting cases, methods of extraction, instruments needed, way and time of delivery after the blood draw.
Concerning the type of the tubes for the blood draw for example is getting more and more necessary that the person who carries out the blood draw must be aware not only for the details of the study but also lately the technical specifications of the tubes they are handling as it is essential for the sustainment of the good quality, the safe transfer and the right preservation of the blood. These studies may detail statistically significant changes in test results over time, but it is important to take into account whether these differences are clinically relevant. Small differences may be tolerated if there is clearly no impact on patient management. Data relating to sample stability may also depend on the tube type used for blood collection, (including any separation gels, anticoagulants and other additives present) the temperature of storage prior to testing, and the laboratory method used for determination. This is particularly true in relation to hemostasis. (e.g. CPT tubes are sensitive in high or very low centrifugation speeds which means that either the tubes are delivered not centrifuged because the medical staff is not aware of these specifications or they are delivered with a broken gel barrier due to high-speed centrifugation or even to a very low one which is just misplacing the gel inside the tube mixing the blood with ingredients for the separation).
Protocol compliance requires a sophisticated organisation with experienced and dedicated investigators who can manage the requirements for the collection and adequate preparation of blood samples, tumor tissues , the molecular and genetic staining of such material, pharmacokinetic sampling at various time points (sometimes well beyond regular working hours), and last but not least the management of patients enrolled in such studies. The fact that such trials are conducted at several centers requires regular communication between sites, the sponsor, and other parties involved. Updates in terms of safety profiles, including potential adjustments to the use of the investigational product during the study, patient slot allocation, and other operational aspects need to be reviewed and discussed on an on-going basis.
Thus, the minimum requirement to qualify as a phase 1 clinical research center is the availability of an experienced principal investigator, who is typically supported by a dedicated sub-investigator. A study co-ordinator ensures that patients are scheduled for the visits according to the study protocol and all necessary evaluations are performed. Such tests are carried out with the support of research or study nurses, who are often also involved in the administration of the investigational product. Storage and preparation of the investigational product are performed in collaboration with the hospital pharmacy. Other departments need to be involved in the conduct of these studies as well, including surgery for tissue collection and referral of patients, pathology for analyses, a laboratory for routine and specialty testing of liquids, and others depending on the nature of the studied disease. In addition, the hospital administration is involved in legal aspects of study contracts with the sponsor and eventually for budgeting purposes.
Delivery time after blood draw is another sensitive point in which the setup must be very detailed and take in consideration the importance of delivering blood samples on estimated time, fear not transportation costs as this affects on the viability and the stability of the blood., in samples participating in an oncology study we are referring in to lost visits of patients that cannot be repeated and in some cases, patients already deceased during the study. The whole essence of an oncology study is the final extraction of PBMCs and their good preservation according to each client’s requirements which is translated in detailed instructions of aliquoting, know how and what is needed to accomplish that scientifically, which is translated for once more in the importance of scientists participating in the procedure of the set up.
Effective and fast communication for troubleshooting cases between both sides involved is becoming more and more needed as this helps in solving out in most of the cases critical points of handling sensitive cells as PBMCs as well as improving procedures through observation in the day by day’s work.
The pharmaceutical industry invests a great deal of time and money educating its associates in drug development. It is of paramount importance that investigators, their research teams, and the investigative institutions be similarly educated in the nuances of developing anti-cancer products if they aim to take part in the drug development process of novel anti-cancer compounds in the future.
1. Dowlati A, Manda S, Gibbons J, et al. Multi-institutional phase I trials of anticancer agents. J Clin Oncol. 2008;26:1926–31. http://dx.doi.org/10.1200/JCO.2007.13.3793. [PubMed] 2. Gajic A, Herrmann R, Salzberg M. The international quality requirements for the conduct of clinical studies and the challenges for study centers to implement them. Ann Oncol. 2004;15(9):1305–9. http://dx.doi.org/10.1093/annonc/mdh363. [PubMed]
Last modified: July 23, 2018