A commendatory word for personalized Medicine (2)

The beginning of the article: A commendable word for personalized medicine (1)ECONOMIC RESEARCH

Personalized medicine provides a new, more profitable economic model for drug development for both pharmaceutical companies and patients.

For example, clinical trials of Herceptin and Glivec, which resulted in the initial regulatory approval of their use, were conducted with the participation of a relatively small number of patients selected for the identification of specific biomarkers. The use of these markers provided more adequate clinical trial results and a faster and less costly way to obtain official FDA approval. Glivec, initially approved for the treatment of chronic myeloid leukemia, was later approved as a treatment for stromal tumors of the gastrointestinal tract, the prerequisite for which was the identification of similar molecular mechanisms of the development of these diseases. Inspired by these success stories, the specialists of several large pharmaceutical companies are currently working on the development of drugs for the treatment of diseases in small populations of patients, which reduces the initial cost and duration of clinical trials. After that, they expand the scope of use of approved drugs for other diseases with similar etiopathogenetic mechanisms (Penny et al. 2005).The results of several studies indicate that molecular diagnostic tests can increase the profitability of medical care.

Based on the processing of insurance claims filed by patients with bronchial asthma, researchers from the Massachusetts Institute of Technology recently studied the economic contribution of hypothetical diagnostic tests in predicting the response to treatment (Stallings et al. 2003). They found that in the case of sufficient, but not excessive sensitivity of the tests, their use would compensate for the costs of the payers for their purchase. In addition, the study of genetic testing for TPMT deficiency, leading to serious adverse reactions to purine drugs, confirmed its profitability under certain conditions (Tavadia et al. 2000; Marra et al. 2002). A pharmacogenomic analysis model detailing the impact of genomic testing of cancer patients on cost savings in the treatment of certain diseases has recently been published (Hornberger et al. 2005).There are still no results of large-scale work devoted to the study of the effectiveness and profitability of treatment methods according to genetic tests.

However, the results of several studies contain a number of interesting facts, as well as a preliminary assessment of the economic benefits provided by personalized medicine in the provision of medical care (Phillips et al. 2005).STATE POLICY

Despite the fact that research and the stable development of science provide arguments in favor of personalized medicine, the results of scientific work are not enough to ensure its implementation in clinical practice.

Factors such as governance, compensation policy, legislative protection against abuse of genetic information, healthcare information technology infrastructure and training of specialists will influence the speed of introduction of personalized medicine into the healthcare system. It is the duty of the Personalized Medicine Coalition and other organizations supporting the new medical direction to support the implementation of strategies that promote the inclusion of personalized medicine in the structure of medical care (Abrahams et al. 2005).Management.

U.S. regulatory authorities support the development of personalized medicine and approve a personalized approach to the development of medicines and diagnostic tools. Over the past few years, the FDA has taken the following actions:– recommended the inclusion of information on the relationship between the genetic constitution and the reaction to the drug in the labeling guide (more detailed information is available on the FDA website);

– approved the first kit for rapid characterization of cytochrome P450 family genes;
– collaborated with other federal agencies to improve cancer treatment methods through the development and evaluation of biomarkers;
– published "Guidelines for the Industry: Presentation of Pharmacogenomic Data", explaining in which case and what type of genome data should be submitted to the FDA, as well as encouraging voluntary submission of genome study results (2005);
– issued a concept document on the joint development of medicinal and diagnostic drugs (2005);
– published guidelines on the introduction of geno- and phenotypic resistance tests in the study of antiviral drugs (2006);
– Issued "Draft Guidelines for the Industry, Clinical Laboratories and FDA staff on Laboratory Diagnostic Multiparameter Kits", with a request for comments from the public (2006)From 2004 (before the publication of the guidelines for the submission of pharmacogenomic data) to the second quarter of 2006, the total number of formal requests (consultations) to the FDA for the analysis and voluntary submission of genomic data increased significantly: from 5 in 2004 to 20 in 2005 and 29 in the first half of 2006 (Frueh 2006).

These actions of the FDA contribute to the creation of a regulatory framework conducive to the development of personalized medicine.

A key regulatory issue that still needs to be worked on is a set of guidelines outlining the requirements for the joint development of pharmacogenomic drugs and diagnostic tests (the concept document and other materials can be found on the FDA website).Compensation.

Adequate and timely coverage of expenses by insurance companies is also very important for the introduction of personalized treatment methods. In many cases, compensation is carried out after the official approval of the drug. For example, the FDA's comprehensive approval of Herceptin and the corresponding test for the identification of breast cancer patients responding to its reception provided the opportunity to compensate for the costs of purchasing both products by most insurance systems. However, strategies for covering expenses and payments need to be adapted in accordance with the development of science. For example, the Medicare compensation policy for diagnostic testing is usually based on the confirmation of a diagnosis based on the identification of traditional signs and symptoms of the disease. This approach may hinder the introduction of molecular tests that provide a higher level of prediction. Compensation strategies need to be reviewed in favor of supporting more predictive, preventive treatment approaches. Medicare's coverage of Herceptin/Herceptest and Oncotype DX gene expression tests portends an increase in payers' awareness of the value of personalized medicine. Updating the prescribing policy in line with the development of personalized medicine is also very important for its recognition by doctors and patients. Modern standard approaches to listing all drugs in pharmacological reference books also need to be revised, taking into account the irrefutable evidence provided by pharmacogenomics that one treatment method cannot be optimal for all patients (Reinhardt 2001).Healthcare information technology infrastructure.

The widespread storage of medical and sanitary documentation in electronic form will play an important role in preparing the healthcare system for the transition to personalized medicine. By providing quick access to clinical information and molecular test results, electronic documents allow doctors and patients to make optimal treatment decisions. The use of an electronic document storage system will also speed up the development of treatment methods by providing researchers with access to large databases (anonymous) about patients. A number of pieces of legislation have already been adopted to ensure the introduction of electronic documentation, while many states, private clinics and practitioners are developing their own information technology programs (Lohr 2006).PRIVACY

Currently, federal and state laws provide only partial protection against the misuse of genetic information.

To realize the potential of personalized medicine, it is necessary to create a legal system for the protection of genetic information based on an approach that excludes discrimination, which will encourage citizens to participate in research and receive all the benefits provided by genetic screening, consultations, testing and new methods of treatment. Proposed legislative documents, such as the "Act on Non-Discrimination of Genetic Information", adopted in 2005, suggest the possibility of eliminating all gaps in the confidentiality system. According to the results of one of the studies (White et al. 2003), almost half of the US population (48%) is interested in using genetic information to improve understanding and optimize their health status. Despite the fact that the general public supports and looks forward to the introduction of personalized medicine into healthcare practice, the fear of genetic discrimination in hiring and obtaining health insurance (68% of respondents) remains a significant obstacle to full public recognition.MEDICAL EDUCATION

The level of practical use of personalized medicine will depend on the awareness of doctors with the theory of the issue and their awareness of existing tests and treatment methods.

Most medical schools do not include personalized medicine in their curricula, which is likely to make it difficult to recognize it in the future (Frueh et al. 2004). On the other hand, specialists will be interested in implementing personalized approaches due to the possibility of using them to improve the level of patient safety, better fulfill their medical duty and reduce treatment costs. It will be necessary to introduce special educational programs to train healthcare workers who are able to use personalized medicine approaches.conclusions

At the present stage, information about personalized medicine is mostly episodic, not statistical, which is absolutely natural, since this medical field is still in its infancy.

In the field of oncology, many proofs have already been received of the expediency of personalized approaches, the number of which is constantly increasing. Many examples demonstrate the value of personalized medicine in selecting the optimal method of treatment, rehabilitation of drugs that have not passed clinical trials and shifting priorities from treatment to disease prevention. Many other claimed benefits have not been proven at the moment, including the possibility of returning previously recalled drugs to the market or reducing the duration, cost and frequency of clinical trial failures. Moreover, there is little convincing evidence of the impact of personalized medicine approaches on the productivity of the pharmaceutical industry and the healthcare economy. It is not yet clear whether personalized medicine will be able to revolutionize clinical medicine. However, at least in a few examples, a personalized approach to treatment has reduced the cost of providing medical care, proved the viability of such an approach to the strategy of developing biopharmacological products and, most importantly, proved its advantages from the point of view of patients. There are already signs that personalized medicine is entering a new phase of development, as evidenced by the appearance of drugs (currently undergoing clinical trials) designed to treat patients who develop resistance to personalized first-generation drugs. Examples include Tykerb and AMN107, designed to replace Herceptin and Glivec, respectively. All this suggests that in the near future the number of successful examples of the use of personalized medicine will increase rapidly.Treatment method

Individual drugs, treatment methods and diagnostic kits provided by personalized medicine (the proposed list, created on the basis of information from research and industrial sources, is not exhaustive, but contains widely used products as of September 2006).

Diagnostic tests that have received official FDA approval and drugs that have a link to pharmacogenomics on the label are highlighted in bold.

BCR-ABL (breakpoint cluster region – Abelson ) – Abelson point break cluster region;
BRCA 1,2 (breast cancer susceptibility gene 1 or 2) – predisposition genes for breast cancer 1 and 2;
c-KIT ( tyrosine kinase receptor ) is a receptor for tyrosine kinase;
CYP (cytochrome P 450 enzyme) – cytochrome P450 enzyme;
HER 2 (human epidermal growth factor receptor 2) is a receptor for human epidermal growth factor-2;
UDP-glucuronosyltransferase – UDP-glucuronosyltransferase.

The article The Case For Personalized Medicine (pdf, 0.5 M) is published on the Personalized Medicine Coalition website.

28.01.2008