After numerous renewals and reignitions since the initiation of the "War on Cancer" more than five decades ago, the recent reignition of "Moonshot to Cure Cancer" points to the systemic persistence of cancer as a major cause of loss of life and livelihood. Literature points to the diminishing returns of cancer research through time, as well as heterogeneities in cancer research centers' innovation strategies. This dissertation focuses on the strategic decision by cancer research centers to invest their resources in conducting early phases of clinical trials on new candidate drugs/treatments (resembling exploration) or late phases of clinical trials that push established candidates towards acquiring FDA approvals (resembling exploitation). The extensive clinical trials data suggests that cancer research centers are not only different in their emphasis on exploratory trials, but also in how their emphasis is changing over time. This research studies the dynamics of this heterogeneity in cancer research centers' innovation strategies, how experiential learning and capability development interact to cause dynamics of divergence among learning agents, and how the heterogeneity among cancer research centers' innovation strategies is affected by the dynamics of learning from experience and capability development.
The findings of this dissertation shows that endogenous heterogeneities can arise from the process of learning from experience and accumulation of capabilities. It is also shown that depending on the sensitivity of the outcome of decisions to the accumulated capabilities, such endogenous heterogeneities can be value-creating and thus, justified. Empirical analysis of cancer clinical trials data shows that cancer research centers learn from success and failure of their previous trials to adopt more/less explorative tendencies. It also demonstrates that cancer research centers with a history of preferring exploratory or FDA trials have the tendency to increase their preference and become more specialized in one specific type (endogenous specialization). These behavioral aspects of the cancer research centers' innovation strategies provide some of the tools necessary to model the behavior of the cancer research efforts from a holistic viewpoint. / Doctor of Philosophy / The "Moonshot to Cure Cancer" was renewed most recently in September 2022. However, renewal and reignition of this national collective effort is nothing new; this effort started as "War on Cancer" in 1971 and has been reignited numerous times. After more than 50 years of our collective battle to cure cancer, it claims almost 600,000 lives annually and remains as the second leading cause of death in the US. There are a wide variety of cancer research centers from all around the world contributing to this collective effort and they make considerably different decisions regarding their investment in research. There is evidence suggesting that some of the research centers' investment decisions are not optimal and can be improved. It has been shown that systems such as patent regulations can be revised to encourage such improved decisions among cancer research centers.
This dissertation focuses on the process of clinical trials for new drugs/treatments for cancer. New drugs/treatments have to pass different phases of trials to ensure that they are safe and effective before they can acquire FDA approvals. Cancer research centers decide whether to invest in early phases of clinical trials for new drug/treatment candidates or invest in late phases of trials for candidates that have already passed the early phases. The clinical trials data show that there has been a sharp rise in number of early phases of trials on new drugs/treatments; however, the same rise cannot be seen in the late phases of trials resulting in approvals. It can also be seen that different research centers put different levels of emphasis on initiating early phases of trials for new drugs/treatments (exploration).
In this dissertation, the hypothesis is that this ongoing dilemma that cancer research centers face to invest on how much emphasis to put on exploration in their clinical trials is affected by learning from experience. To test this hypothesis, a mathematical model is used to show differences in decisions can be causes solely by learning from experience, when the decision maker is learning "what to do" from success/failure of previous efforts and learning "how to do it" from practicing and accumulating the required skills. Then, the hypothesis is formally tested using the clinical trials data. The results show that cancer research centers learn from the success and failure of their previous exploratory trials when deciding on their emphasis on exploration. Also, they accumulate skills, resources, and capabilities relevant to the type of research the conduct more often and specialize in either of late- or early-phases of trials.
The findings of this dissertation show that learning from experience can cause in differences in decisions. It also finds evidence that cancer research centers learn to place different levels of emphasis on exploration in their clinical trials. These findings can later be used in models of the cancer research ecosystem to study how funding structures and policies can be changed to improve the outcomes of our collective effort to cure cancer.
| Identifer | oai:union.ndltd.org:VTETD/oai:vtechworks.lib.vt.edu:10919/116191 |
| Date | 01 September 2023 |
| Creators | Mahmoudi, Hesam |
| Contributors | Industrial and Systems Engineering, Ghaffarzadegan, Navid, Triantis, Konstantinos P., Rahmandad, Hazhir, Hosseinichimeh, Niyousha |
| Publisher | Virginia Tech |
| Source Sets | Virginia Tech Theses and Dissertation |
| Language | English |
| Detected Language | English |
| Type | Dissertation |
| Format | ETD, application/pdf |
| Rights | In Copyright, http://rightsstatements.org/vocab/InC/1.0/ |
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