Developments in Genetic Testing, Current Trends, and the Future of Precision Medicine
Breakthrough biologic treatments for targeted populations are on the horizon, but ethical issues and current disparities limit our potential.
Precision medicine makes inroads into clinical trials through Precision Promise.
Precision Medicine, also known as personalized medicine, is patient-centered medicine that takes into consideration the genetic makeup, lifestyle, and environment of each patient when determining a course of treatment. This differs from traditional treatment which tries to treat large diverse populations with a “one-size-fits-all” medication. (Center for Devices and Radiological Health, 2018).
Most precision-based medications which have been submitted to and approved by the FDA have been for the treatment of cancer. Just last week, the Pancreatic Cancer Network launched Precision Promise, a precision-medicine-based clinical trial.
The first trial of its kind, patients will be assigned a course of treatment after undergoing advanced molecular profiling. The study will be conducted inclusive of the concepts of precision medicine. During the study, if the arm of treatment a patient is originally assigned to is deemed ineffective, the patient will be switched to an alternative line of treatment. (Intelligence, 2021).
The results gathered will be analyzed by research teams to improve pancreatic cancer drugs. The first of its kind, an adaptive clinical trial, allows investigators to quickly gather information on fewer subjects in less time than in traditional clinical trials. The hope is that this will lead to faster approvals for the most effective treatments. (Pancreatic Cancer Action Network, 2020).
Research shows that patients in clinical trials for pancreatic cancer fare better than those who do not.
The initial data from the trial through 2020 shows that patients undergoing treatment that matches the biology of their tumor live an average of one year longer than those who were unable to enter the precision-medicine-based trial. Research also shows that those who enter a clinical trial for pancreatic cancer have better outcomes. Those who do not enter a clinical trial have a 5-year survival rate of just 10%. (Pancreatic Cancer Action Network, 2020).
Yet, due to poorly designed clinical trials, an inability to reach those patients in need, clinical trials with prohibitive exclusionary criteria, a general mistrust and/or misunderstanding of clinical research, and doctors as well as patients not having access to current information regarding accessible clinical trials in their area, only 4% of pancreatic cancer patients enter clinical trials. (Pancreatic Cancer Action Network, 2020).
Advances in Next Generation Sequencing (NGS) hold potential for better treatment in a wider variety of therapeutic areas.
Precision-medicine-based therapy is just beginning to grow outside of Cancer, and Alzheimer’s and Parkinson’s disease research and treatment. Researchers in the field of mental health are also taking an interest in the potential benefits precision medicine can offer their patients. Recent advances in Next Generation Sequencing (NGS) tests have identified 19 genes and 25 proteins which play a role in the development of depression. Continued blood tests identifying blood biomarkers can contribute significantly to future clinical trials developing personalized medicines matching the genetic needs of a specific set of patients. (Kent, 2021).
NGS tests are one of the latest tools available to researchers enabling them to quickly sequence and identify large sections of a person’s genome which can be analyzed for mutations and variants informing them of which treatment options will work best for a specific patient. NGS tests in addition to diagnosing and treating patients are also contributing to the understanding of various diseases furthering our advancements when considering avenues to pursue for future treatments. (Center for Devices and Radiological Health, 2018).
Covid-19 shines a light on racial disparities in clinical trials.
Demand for precision medicine treatments has been surging since the beginning of the Covid-19 pandemic. Since people who contract Covid-19 have been manifesting a wide variety of symptoms as people react differently to the infection. Racial disparities and inequalities in access to health care have been exacerbated by Covid-19.
According to the study Equity in Health: Consideration of Race and Ethnicity in Precision Medicine, “The age-adjusted COVID-19 mortality rate is greatest among African-American/black individuals (133.5 per 100 000) compared with Latino (93.6 per 100 000) and European ancestry/white (49.4 per 100 000) individuals.” (Todd, 2020).
Thus far, advances in the field of precision medicine have made advances most beneficial to those of European descent, the disparity in clinical trial participants being identified as the root cause. Over 75% of clinical trial participants are of European origins. Lack of access to proper health care, mistrust of clinical trials based on historical and familial reasons, as well as protocols that exclude many African Americans due to restrictive limits of inclusion based on Body-Mass Index (BMI) have severely hampered genetic research for non-white populations. (Edwards et al., 2020).
The American Association for Cancer Research when analyzing the disparities in cancer research due to race and ethnicity stated that “34% of all deaths from cancer in those aged 25 to 74 could be prevented by 2035 if disparities in access to care were eliminated; and that from 2003 to 2006, disparities cost the nation $230 billion in direct medical costs, and indirect costs to society were more than $1 trillion.” (Caffrey, 2021).
Medicare representative Dr. Debra Patt stated that “multiple factors, including biologic ones, contribute to disparities in health and cancer outcomes. Black patients are more likely to have aggressive breast and prostate cancer and multiple myeloma, while Hispanic populations are likely to have higher rates of cervical and hepatobiliary cancers. But as a physician in 1 of 12 the states that have not expanded Medicaid, geography plays a role, too.” (Caffrey, 2021).
Pratt went on to state that 1 in 4 Texans do not have access to health insurance while the predominately minority members of that socioeconomic class are 6 times more likely to present with advanced cancer dying earlier than the majority white population who more often get diagnosed earlier and are more likely to seek treatment. She continued, “If patients in minority groups have less access to care and are underrepresented in trials, then they are also underrepresented in genome-wide association studies that are used in drug development.4 According to a recent study, the degree to which they are underrepresented is astonishing: By 2017, of 35 million samples, 80% were of Northern European ancestry, even though this population is less than 10% of the population worldwide.” (Caffrey, 2021).
Emerging data from precision medicine will assist telemedicine health providers to adequately target their specific patients’ needs.
The emerging trend towards telemedicine, also brought about by Covid-19 while people were quarantined as many still are, also is showing an increased interest in precision medicine. In short visits with many new patients, advances in NGS and precision medicine can assist doctors in telemedicine to quickly and accurately diagnose their patients while providing for a more personalized course of treatment enabling them to provide a specific medication which works best for that individual patient. (Intelligence, 2021).
Yet, even with the disparities in representation of minority groups, there is a vast amount of NGS data being given to the FDA presenting them with novel regulatory issues. The most potentially negative of these issues being the protection of patient safety and privacy as a government agency compiles a genetic database of the American population as a natural side-effect of the normal process of the conduct of clinical research. (Edwards et al., 2020).
The need for data for treatment runs into patient privacy protection.
Kyle Brothers and Mark Rothstein point out that,
“There are three main reasons why the protection of informational health privacy is so important. First, individuals may suffer from embarrassment, stigma, discrimination, and other harms to their dignity if sensitive information is inappropriately disclosed. Second, the quality of healthcare may be compromised if individuals who fear improper disclosure of their sensitive information forego timely treatment for stigmatizing conditions or engage in defensive practices, such as withholding certain information from their healthcare providers Third, public health harms may occur if individuals with infectious diseases, mental illness, substance abuse or other sensitive conditions delay or decline treatment because they fear a loss of privacy.” (Brothers & Rothstein, 2015).
For most of those diagnosed with a deadly or debilitating disease, the benefits of personalized medicine far outweigh the potential negative consequences associated with the possible harmful results of bad actors gaining access to their personal health and genetic data. This will present several ethical and legal challenges for the FDA as advances in NGS testing are made.
The implications for society in the near future are profound. Significant changes in health insurance policies and coverage, laws, and regulations addressing the conduct of clinical trials, as well as security and privacy challenges surrounding the protection of the population’s privacy and each person’s genetic information to prevent misuse or abuse of that data are seriously significant issues that will need to be addressed soon.
References
Center for Devices and Radiological Health. (2018, September 27). Precision Medicine. U.S. Food and Drug Administration. https://www.fda.gov/medical-devices/in-vitro-diagnostics/precision-medicine
Brothers, K. B., & Rothstein, M. A. (2015). Ethical, legal, and social implications of incorporating personalized medicine into healthcare. Personalized Medicine, 12(1), 43–51. https://doi.org/10.2217/pme.14.65
Caffrey, M. (2021, April 22). Disparities in Cancer Care: Has Precision Medicine Widened the Gap? AJMC. https://www.ajmc.com/view/disparities-in-cancer-care-has-precision-medicine-widened-the-gap-
Edwards, T., Breeyear, J., Piekos, J., & Velez Edwards, D. R. (2020). Equity in Health: Consideration of Race and Ethnicity in Precision Medicine. Science & Society, 11(11), 807–809. https://www.cell.com/trends/genetics/fulltext/S0168-9525(20)30167-0?_returnURL=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS0168952520301670%3Fshowall%3Dtrue
Intelligence, P. (2021, March 29). Precision Medicine Market Revenue Worth $738.8 Billion by 2030: P&S Intelligence. Precision Newswire. https://www.prnewswire.com/news-releases/precision-medicine-market-revenue-worth-738-8-billion-by-2030-ps-intelligence-301256580.html
Kent, J. (2021a, April 15). How Precision Medicine Approaches Could Impact Mental Healthcare. HealthITAnalytics. https://healthitanalytics.com/news/how-precision-medicine-approaches-could-impact-mental-healthcare
Kent, J. (2021b, April 19). Clinical Trial Uses Precision Medicine for Pancreatic Cancer Drugs. HealthITAnalytics. https://healthitanalytics.com/news/clinical-trial-uses-precision-medicine-for-pancreatic-cancer-drugs
Kimmel, P. L., Fwu, C. W., Abbott, K. C., Ratner, J., & Eggers, P. W. (2016). Racial disparities in poverty account for mortality differences in US medicare beneficiaries. SSM — Population Health, 2, 123–129. https://doi.org/10.1016/j.ssmph.2016.02.003
Pancreatic Cancer Action Network. (2020, April 1). RE: An overview of PanCAN and PanCAN research efforts [Press release]. https://www.aacr.org/wp-content/uploads/2020/04/PanCAN_AACR_Publications-Letter_2020-1.pdf
Pancreatic Cancer Action Network. (2021, April 13). Pancreatic Cancer Action Network — Research, Patient Support, Resources. https://www.pancan.org/
Precision Medicine: Technology, Regulations and Challenges. (2016, March 11). RAPS. https://www.raps.org/regulatory-focus%E2%84%A2/news-articles/2016/3/precision-medicine-technology,-regulations-and-challenges