Pharmacogenomic technologies: a necessary "luxury" for better global public health?

Abstract

BackgroundPharmacogenomic technologies aim to redirect drug development to increase safety and efficacy of individual care. There is much hope that their implementation in the drug development process will help respond to population health needs, particularly in developing countries. However, there is also fear that novel pharmacogenomic drugs will remain too costly, be designed for the needs of the wealthy nations, and so constitute an unnecessary "luxury" for most populations. In this paper, we analyse the promise that pharmacogenomic technologies hold for improving global public health and identify strategies and challenges associated with their implementation.DiscussionThis paper evaluates the capacity of pharmacogenomic technologies to meet six criteria described by the University of Toronto Joint Centre for Bioethics group: 1) impact of the technology, 2) technology appropriateness, 3) capacity to address local burdens, 4) feasibility to be implemented in reasonable time, 5) capacity to reduce the knowledge gap, and 6) capacity for indirect benefits. We argue that the implementation of pharmacogenomic technologies in the drug development process can positively impact population health. However, this positive impact depends on how and for which purposes the technologies are used. We discuss the potential of these technologies to stimulate drug discovery in the case of rare (orphan diseases) or neglected diseases, but also to reduce acute adverse drug reactions in infectious disease treatment and prevention, which promises to improve global public health.ConclusionsThe implementation of pharmacogenomic technologies may lead to the development of drugs that appear to be a "luxury" for populations in need of numerous interventions that are known to have a demonstrable impact on population health (e.g., secure access to potable water, reduction of social inequities, health education). However, our analysis shows that pharmacogenomic technologies do have the potential to redirect drug development and distribution so as to improve the health of vulnerable populations. Strategies should thus be developed to better direct their implementation towards meeting the needs and responding to the realities of populations of the developing world (i.e., social, cultural and political acceptability, and local health burdens), making pharmacogenomic technologies a necessary "luxury" for global public health.

Pharmacogenomics in Early-Phase Clinical Development

“…Such ‘rescuing’, ‘resuscitation’ and ‘repurposing’ of drugs has been proposed by the NIH as a key initiative in the fight against stagnation in drug development [11,69]. Finally, PGx technologies may facilitate development of drugs for vulnerable populations and rare diseases, reduce ethnic disparities in applications of research findings and contribute to improved global public health [44]. …”

“…This could translate into better public health benefits and eventually reduced hospitalizations and burden of illness, and increased productivity of affected individuals [33,41–43]. PGx has the potential to improve the health of vulnerable populations and neglected diseases [44]. Nevertheless, the application of PGx knowledge and principles in clinical practice has been slow [4,32,37,45–48].…”

“… Identifying drug targets – those relevant to the drug’s efficacy, safety, pharmacokinetics Study design [98]: Outcomes that could be impacted by genotype variability: Pharmacokinetics – area under the curve, C max , T max , clearance, volume of distribution, half-life, trough drug concentrations [10] Pharmacodynamics – biomarkers related to efficacy and/or toxicity [99] Drug–drug interactions Clinical outcomes – response, remission and other global measures not directly associated with specific biomarkers Dose selection – influenced by existing population and subpopulation information on dose–response and concentration–response relationships of genes relevant to the drug or disease under study [10,100] Therapeutic window for the drug: identifying drug plasma concentrations that are between toxic levels (upper limit) and non-effective levels (lower limit) Selection of participants (i.e., contributing to more meaningful inclusion/exclusion criteria) – for example: inclusion of ethnic or other subpopulations with known genetic variants relevant to drug response (e.g., apoE [101]) Prospective selection of covariates to understand gene-covariate impact on variability [10] Statistics – exploratory and hypothesis-generating approach is the rule in early-phase studies Ethics: adhering to pharmacogenomic principles would enable more ethical study designs by limiting the testing of new medications to those most likely to benefit and least likely to experience adverse outcomes Acquisition of information and expertise required to design future studies (i.e., Phase III and Phase IV) Potential for genotype-specific regulatory approvals and product labeling [29,69,102] Drug ‘rescue’ and ‘repurposing’ Vulnerable population and rare disease drug development [44] …”

Global pharmacogenomics: Where is the research taking us?

“…Other promises include increased efficiency in drug development through the ability to identify those patient sub-groups most likely to benefit from a drug and so to include in clinical trials, and those who might be at risk and so should be excluded from potentially dangerous trials. The resulting cost-savings of safer and more efficient clinical trials could then create an incentive for pharmaceutical companies to develop drugs for a wider range of diseases, including those that are rare or have been neglected (Olivier, Williams-Jones, Godard, Mikalson, & Ozdemir, 2008;Olivier & Williams-Jones, 2011;Pang, 2003). Yet, the success of pharmacogenomics drugs or other interventions have thus far been mitigated (Ma & Lu, 2011).…”

Microarray Based Pharmacogenomics Study Of Celecoxib On Breast Cancer Samples

“…It is marketed by Pfizer under the brand name Celebrex. In some countries, it is branded Celebra [8].…”