Personalized Medicine: Ethics for Clinical Trials

Author(s):  
G. Terry Sharrer
2019 ◽  
Vol 25 (2) ◽  
pp. 95-105
Author(s):  
Agata Blasiak ◽  
Jeffrey Khong ◽  
Theodore Kee

The clinical team attending to a patient upon a diagnosis is faced with two main questions: what treatment, and at what dose? Clinical trials’ results provide the basis for guidance and support for official protocols that clinicians use to base their decisions upon. However, individuals rarely demonstrate the reported response from relevant clinical trials, often the average from a group representing a population or subpopulation. The decision complexity increases with combination treatments where drugs administered together can interact with each other, which is often the case. Additionally, the individual’s response to the treatment varies over time with the changes in his or her condition, whether via the indication or physiology. In practice, the drug and the dose selection depend greatly on the medical protocol of the healthcare provider and the medical team’s experience. As such, the results are inherently varied and often suboptimal. Big data approaches have emerged as an excellent decision-making support tool, but their application is limited by multiple challenges, the main one being the availability of sufficiently big datasets with good quality, representative information. An alternative approach—phenotypic personalized medicine (PPM)—finds an appropriate drug combination (quadratic phenotypic optimization platform [QPOP]) and an appropriate dosing strategy over time (CURATE.AI) based on small data collected exclusively from the treated individual. PPM-based approaches have demonstrated superior results over the current standard of care. The side effects are limited while the desired output is maximized, which directly translates into improving the length and quality of individuals’ lives.


2006 ◽  
Vol 7 (7) ◽  
pp. 1087-1094 ◽  
Author(s):  
Jan van der Greef ◽  
Thomas Hankemeier ◽  
Robert N McBurney

2015 ◽  
Vol 5 (4) ◽  
pp. 415-425 ◽  
Author(s):  
Feifang Hu ◽  
Yanqing Hu ◽  
Wei Ma ◽  
Lixin Zhang ◽  
Hongjian Zhu

2020 ◽  
Author(s):  
Rich Colbaugh ◽  
Kristin Glass

AbstractThere is great interest in personalized medicine, in which treatment is tailored to the individual characteristics of patients. Achieving the objectives of precision healthcare will require clinically-grounded, evidence-based approaches, which in turn demands rigorous, scalable predictive analytics. Standard strategies for deriving prediction models for medicine involve acquiring ‘training’ data for large numbers of patients, labeling each patient according to the outcome of interest, and then using the labeled examples to learn to predict the outcome for new patients. Unfortunately, labeling individuals is time-consuming and expertise-intensive in medical applications and thus represents a major impediment to practical personalized medicine. We overcome this obstacle with a novel machine learning algorithm that enables individual-level prediction models to be induced from aggregate-level labeled data, which is readily-available in many health domains. The utility of the proposed learning methodology is demonstrated by: i.) leveraging US county-level mental health statistics to create a screening tool which detects individuals suffering from depression based upon their Twitter activity; ii.) designing a decision-support system that exploits aggregate clinical trials data on multiple sclerosis (MS) treatment to predict which therapy would work best for the presenting patient; iii.) employing group-level clinical trials data to induce a model able to find those MS patients likely to be helped by an experimental therapy.


2011 ◽  
Vol 29 (15_suppl) ◽  
pp. CRA2500-CRA2500 ◽  
Author(s):  
A. M. Tsimberidou ◽  
N. G. Iskander ◽  
D. S. Hong ◽  
J. J. Wheler ◽  
S. Fu ◽  
...  

2011 ◽  
Vol 29 (18_suppl) ◽  
pp. CRA2500-CRA2500 ◽  
Author(s):  
A. M. Tsimberidou ◽  
N. G. Iskander ◽  
D. S. Hong ◽  
J. J. Wheler ◽  
S. Fu ◽  
...  

CRA2500 Background: We initiated a personalized medicine program hypothesizing that tumor molecular analysis and use of targeted therapy to counteract the effects of specific aberrations would improve the outcomes of affected patients. Methods: Molecular analysis was performed in the M. D. Anderson CLIA-certified pathology laboratory. Patients whose tumors had an aberration were treated in the Phase I Program with a matched targeted agent, when available. Results: Tumor molecular analysis was feasible in 852 (89%) of 955 consecutive patients with advanced cancer. Of 852 patients (median, age 56 yrs; prior therapies 4), 354 (41.5%) had ≥ 1 aberration: 10% of patients had a PIK3CA mutation; 19% KRAS; 8% NRAS; 19% BRAF; 3% EGFR; and 2% had a CKIT mutation; 21% had PTEN loss. Results are shown in the table. Median time to treatment failure (TTF) in 161 patients with 1 aberration treated with matched targeted therapy was 5.3 months (95%CI: 4.1, 6.6) vs 3.2 months (95%CI: 2.9 – 4.0) for their prior systemic antitumor therapy (prior to referral to phase I) (p= .0003). For patients with 1 aberration, the CR+PR rate was 29% with matched targeted therapy vs. 8% without matching (p = .0001). The CR+PR rate was 6% in 438 patients without molecular testing treated on the same studies. Conclusions: Preliminary results suggest that in early clinical trials matching patients with targeted drugs based on their molecular profile results in (a) longer TTF compared to their prior therapy and (b) higher rates of response, survival and TTF compared to those seen in patients treated without molecular matching. Support: 3UL1 RR024148 04 S1 and IPCT. [Table: see text]


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