Personalized Medication in Germany

Personalized Medication in Germany

Introduction

Personalized medicine represents a transition from the usual generalization technique applied to the treatment and care of patients with specific conditions to one which utilizes new technologies for better management of patients’ health. It aims at therapies to attain the best outcome in the management of a patient’s disease or disease predisposition. Humans are unique beings. Human health is determined by innate differences combined with their environment and lifestyle. This essay recognizes that through a combination of an analysis of information about human genome, with diagnostic and clinical information, patterns can be discovered that assist in determining each individual’s risk in the development of a particular disease, earlier detection of illness and identify the most effective measures of intervention to assist in health improvement either through simple diet changes, choices of lifestyle, and medicines.

The idea of personalized medicine has been in existence for a long time. There has been an active effort by clinicians to personalize care carved to people’s individual health needs throughout medical history. However, it has not been possible to predict how individual bodies might react to particular interventions or in identifying persons who might be at the most risk. There has been an emergence of new possibilities through a combination of new technologies such as wearable technology, data and informatics, and whole-genome sequencing. The interconnectedness between these innovations makes it possible to realize the era of truly personalized care.

In 2003, the Human Genome Project (HGP) was completed in 2003, and the quickly decreasing human genome costs facilitated the development of a new medical technique which is called personalized medicine (PM). Scientific and technological advances are already driving human society and will continue to improve and develop medical practice; change is, as they say, is inevitable. Germany should consider not whether the country adapts personalized medicine but how the health care system can best respond and adapt, ensuring every person stands to benefit despite their residential area, illness, or the place of care provision. Germany is on a pathway to developing a personalized medicine approach into mainstream healthcare. There are already deliberations as to the meaning of personalized medicine and how it will work now and in the future. The discussion also involves the technique that will be used, and also how to ensure that economic, equality, and ethical considerations are fully understood and addressed.

Through a groundbreaking global initiative, 100,000 Genome Project, a groundbreaking and world-leading initiative, the establishment of collaborations with industry and academia to decode the human genome in people with rare cancer and other diseases will prove significant. This will assist in the prediction of future development of disease to make a previously non-existent diagnosis and identify treatments where possible.

The term personalized medicine began to be used in the late 1990s and was heavily marked by pharmacogenomics and the promise of developing adequate drugs for the genetic characteristics of population subgroups. However, the meaning has evolved where some authors are in defense of a more comprehensive approach, including molecular and genetic information, including clinical data, diet, lifestyle, and other biomarkers. The European Science Association took another approach to personalized medicine, where it defined it as follows.

”A new approach to classifying, understanding, treating, and preventing disease based on individual biological and environmental differences. It seeks to integrate data on the entire dynamic biological makeup of each individual as well as the environmental and lifestyle factors that interface with this makeup to generate a complex, individual phenotype”.

The complexity of the disease process in the common non-communicable diseases has raised several skepticisms. Unlike monogenetic diseases, most of the non-communicable diseases are caused by complexities of interactions several genes with factors within the environment, creating a major challenge for the realization of PM. However, PM still has little to offer in terms of the treatment of complex multifactorial diseases, except the field of oncology.

Since 2005, complete genomic sequencing became more accessible; thus, it became faster and less expensive with the introduction of a new generation sequencing. However, it has not proven useful in the clinical practice except for rare genetic diseases where it is used for purposes of diagnostics, avoiding the need for patient transfer from one specialist to another, and the need for several tests to attain a diagnosis. Gene therapy, which includes genome editing, has garnered significant momentum since the development of the CRISPR/Cas9 system (Clustered Regularly Interspaced Short Palindromic Repeats) in 2012. This instrument has been revolutionary considering its low cost, precision, speed, and ease of use with a vast potential for the PM to put in place a pathway to correcting genetic mutations in rare and complex diseases. CRISPR/Cas9 performs its role as a scissor that can identify and cut segments of DNA pasting or replacing pieces of genetic code. The pharmaceutical industry is heavily investing in research of its use in clinical practice; however, several technical obstacles need to be dealt with to achieve its full therapeutic potential.

In terms of predictive tests, defenders of PM usually refer to the genetic tests for the BRCA1 and 2 mutations, which indicated to assess the risk of developing hereditary ovarian cancer and breast cancer as a successful example of tests that can indicate lifetime risk of sixty-five percent for ovarian cancer and eight-five percent for breast cancer. These tests present a suggestion about the greater frequency of mammograms, chemotherapy, and prophylactic surgery and identifying other members of the family who are at risk. Despite the availability of these tests for clinical practice since the mid-1990s, they have garnered great visibility after the announcement by Angelina Jolie in 2013 that she was a carrier of the BRCA1/2 gene mutations and had gone through a prophylactic mastectomy. The “Angelina Jolie effect” saw an increase in demand for BRCA1/2 tests by women from several countries, but it did not lead to a subsequent increase in the rates of mastectomy. Media and celebrities have a huge influence on the behavior of patients; however, questions have been raised about the need to provide the public with necessary high-quality information to prevent the oversupply of tests from individuals with low risks.

The concerns of tests arise due to the increased supply of genetic tests directly to consumers through companies like Miroculus, uBiome, and 23andMe. For instance, 23andMe performs genetic tests to inform people about their genetic and ancestry susceptibilities, measuring risks for a series of conditions such as hereditary hemochromatosis, Alzheimer’s disease, Parkinson’s disease, hereditary thrombophilia, and macular degeneration. The procedure entails the consumer ordering for the kit online, and the company later mails it. The consumer collects the sample at home and submits to the company by mail, where they get results several weeks later. In 2018, the Food and Drug Administration (FDA) announced the approval of 23andMe for the direct marketing of BRCA1/2 to consumers with no need for medical prescription or genetic counseling. This approval announcement raised criticism from physicians and researchers regarding, who informed the public that the commercial test was only limited to the identification of genetic variants found in Ashkenazi Jewish Women and rare among the overall population.

Although companies expressed enthusiasm in marketing the genetic tests, the promise of estimating genetic susceptibility based on polymorphisms for complex diseases such as schizophrenia, depression, cardiorespiratory diseases, diabetes, and cancer have not yet materialized. Research on Full Genome association has pointed to the modest associations of genetics with a slight increase in the risk of disease and the little predictive value when compared to the contributions behavioral and social factors, family history, and environmental risks. Companies marketing the genetic susceptibility tests are performing a reinterpretation of genome-wide association studies (GWAS), by utilizing the results of statistical associations between genetic variants and health outcomes in populations as though they were able to predict the risk on each individual.

The assumption that PM will lead to a person adopting preventive measures based on the knowledge of their genetic vulnerabilities is also an emerging concern. Research shows that information about genetics does not lead to a change in behavior y the individuals who are at risk. Supporters of PM, however, continue to overlook the low effect of an action directed towards high-risk individuals.

The new genomic technology seeking to find out the molecular profile of tumors, utilization of targeted drugs, and immune therapy, is best applied in the field of oncology where it has been regarded as successful. Several types of cancer have shown a good response to treatment from targeted drugs. Breast cancer treatment has been completely transformed through trastuzumab associated with the genetic test for tumors that express the HER2 protein and imatinib in the treatment of chronic myeloid leukemia (CML) leading to clinical improvements for patients. For instance, in the treatment of colorectal cancer, patients who receive chemotherapy and cetuximab reveal a better response therapy than those only on chemotherapy. However, this is with the exception of patients with the gene variation (mutant KRAS) fail to benefit from the drug.

Women with breast cancer can be spared from more aggressive approaches to treatments such as chemotherapy through gene panels. In 2018, TAILORx study referred to as Oncotype DX Breast Cancer Assay managed to safely identify women who had early-stage breast cancer could benefit from hormone therapy and avoid chemotherapy. About seventy percent of patients with early-stage cancer could avoid chemotherapy.

A more recent and promising cancer treatment technology referred to as immune therapy and used in the simulation of the immune system of the patient, where it recognizes and eliminates the tumor. PD-1 and CTLA-4 are the regulators of the negative immune response being acted on by antibodies, which showed a significant improvement in long-term survival, particularly in melanoma. Ipilimumab was among the first drugs and began reaching the market in 2011, followed by a more effective second generation of drugs such as pembrolizumab and nivolumab.

However, the progress illustrated may represent only a single side of the coin. High levels of enthusiasm have dominated history of the immune therapy in cancer following unreliable case reports showing only cases of the huge success of the therapy. However, these gains might be incremental but are limited to a distinctly small group of patients with a particular type of cancer.

Concerning targeted drugs, the evolution inspired by drugs such as imatinib and trastuzumab did not materialize. Yet, they are among the few types of target therapy that led to long-term improvement with single agents. Most of the new target drugs have not achieved the same benefits as their predecessors. Moreover, with seventy, one new drug approved by the FDA  for the treatment of cancer from 2002 to 2014 only had a mean improvement of two-point months.

The major challenge brought about by the resistance of the targeted drugs was due to clonal evolution and tumor heterogeneity, which exist in several cancers. With regards to the analysis of the tumor mutations, targeted drugs only get rid of the vulnerable clones, leaving behind the resistant and adapted cells alive, causing resistance to the drugs. Targeted therapies such as BRAF(V600) are effective in dealing with tumors leading to significant clinical improvements; however, it is usually short-term, leading to the rapid adaptation of tumors, thus drug resistance.

Based on the recently available evidence, it will only be prudent to apply a moderate tone when it comes to PM. Although PM may not be as revolutionary in the medical sector, it may facilitate an incremental gain on particular cases as a witness by particular types of cancer. It would be imprudent to generalize the penetration of genomic technology in medicine, there are other areas in which technology has not yet penetrated, and even in the field of oncology, there are several types of cancers in which genomic technology has not led to any significant progress.

The great promises of precision medicine are the reduction of cost of medical care due to greater efficiency in drug use, and only using drugs to the appropriate patients. This promise has not been realized; in contrast, the high cost of targeted drugs produces inequalities in the access to drug’s benefits and challenges for the sustainability of the health system. The cost of new cancer drugs is rising each year, and this is due to drugs that need to be combined to attain the best results clinically. For instance, it is quite expensive to combine ipilimumab (anti-CTLA4) and nivolumab (anti-PD-1). Despite the availability of generic drugs, the prices of drugs have failed to reduce overtime.

The major elements in the rising costs of cancer treatments can be due to the rising cost of new drugs, which only have little benefits for the patients. Scholars believe that the production of high-cost drugs for only little benefits cannot be sustained for long. Target drugs may have several benefits, but new intervention strategies have not been adequately assessed. According to the European Medicine Agency (EMA) examination of cancer treatment drugs between 2009 and 2013, showed that many drugs entered the market without any evidence of benefit in terms of quality of life or survival.

Personalized medicine has done well in keeping its promise of compensating private investment in the biotechnology and pharmaceutical industry instead of the provision of savings for health services. This means that technology and research could facilitate the reduction of health services costs but would put corporate profitability under risk; thus, the loss of the production of high-cost drugs.

One of the problems identified by PM critics relates to the level by which the scientific community, the government, the pharmaceutical industry, and funding agencies is changing the priorities of research and directing them to lower levels of attention to social health determinants and preventive measure that may have an effect on the population. In the last ten years, public health funding has reduced in the last decade, while genomic research funding continues to grow substantially.

If the principal foundation of the underlying social causes of the problems brought about by PM is not effectively addressed, public health problems will continue to sustain. The great achievements in the improvement of population health indicators were contributed to through improvements in the socio-economic conditions and key factors for population groups such as the tobacco control program, vaccination, and basic sanitation. The priority approach taken by PM emphasizes on high-cost drugs set only to benefit small populations but will fail to produce an impact on the greater population, including overlooking of low-cost and more effective population intervention and policies. Moreover, PM leads to an exaggerated optimism with promises brought about by PM. For instance, patients are already visiting offices of physicians asking for a prescription of a new drug they might have come across on the internet. Thus, this may lead to a generation that perceives the world through individualistic lenses.

PM continues to be very controversial, leading to heated debates. High expectations have been established through the promises of PM regarding the potential of new molecular and genomic technologies for the prevention and treatment of complex diseases. However, more restraint and caution are necessary with regard to the promises of personalized medicine. As much as there have been successes in the know-how of molecular mechanisms of diseases and the development of drugs with a significant impact on the treatment of several types of cancer, these achievements cannot be interpreted as evolutionary since evidence suggest that their reproduction in complex diseases is minimal.

Conclusion

The major focus on the individual and the high cost of technologies that only benefit a small population proportion will fail to reduce the major problems of health affecting the world but may contribute to the increase of inequalities with a concentration of technologies and resources in the population section that already has the means to access the best healthcare. This will only magnify the problem of health inequalities preventing the sustainability of health services, particularly in low income or middle-income countries. A cost-benefit assessment is necessary before the integration of new technologies in PM; this should be done from an ethical standpoint that considers the accessibility to everyone preventing the inequalities in healthcare access.