- Personalized medicine has increasingly become the focus of health research and health policy in recent decades. It promises customized treatment by making a risk-benefit decision before choosing a therapy. This results in greater therapeutic success and fewer side effects.
- The topic of personalized medicine is primarily associated with pharmaceutical progress and drug innovations. However, the prerequisite and core element of personalized medicine is targeted diagnostics.
- The importance of laboratory diagnostics for the beneficial use of personalized medicine is not limited to the important function of companion diagnostics. It also covers a wide range of applications in diagnosis, therapy monitoring, prognostic and predictive information and risk analysis in the case of genetic predispositions. The indications addressed range from oncological diseases to autoimmune diseases and infectious diseases.
- As personalized medicine will continue to gain in importance, the reimbursement system must be further developed and made future-proof. In particular, the SGB V regulations on the reimbursement of companion diagnostics should be adapted so that the diagnostics are reimbursed at the same time as the drug is reimbursed and not six months later. The framework conditions for studies cannot simply be transferred from the pharmaceutical sector, but should correspond to the conditions and possibilities in diagnostics. In order to make laboratory innovations patient-centered, health data should also be made available for secondary use for the purposes of industrial research.
Personalized medicine is a multifaceted term
Personalized medicine is increasingly becoming the focus of health research and health policy. It promises customized treatment and thus greater therapeutic success and fewer side effects. In addition to the great benefits for the individual patient, personalized medicine contributes to a more cost-efficient use of resources in the healthcare system, for example by avoiding costly misguided therapies. While some see personalized medicine as a beacon of hope, others warn against exaggerated expectations. Intensive research in recent years has led to a better understanding of the molecular causes of diseases. From this, starting points for diagnostics and therapy can be identified. Progressive molecular differentiation primarily affects oncological, neurological and immunological diseases. The recognition of more and more correlations in molecular diagnostics goes hand in hand with the generation of large, complex and changing amounts of data. Their processing (big data) is becoming increasingly important and is a critical success factor in this area.
The term personalized medicine - the terms individualized or stratified medicine and precision medicine are often used synonymously - is often associated with the expectation that medical interventions will be researched and developed in the sense of individual medicine for a single person. However, this "tailor-made suit" only rarely corresponds to current possibilities. Rather, personalized medicine forms subgroups of patient populations on the basis of genetic, molecular or cellular characteristics of the patients. This stratification leads to differentiated treatment based on a diagnosis that is optimized in terms of precision and control effect. The therapeutic "one size fits all" is replaced by "ready-made sizes".
Advanced therapy medicinal products (ATMPs) are also part of personalized medicine. They include applications that are based on genes, tissues or cells and are actually tailored to the individual. The development and use of ATMPs in medical care also require special laboratory diagnostics. However, ATMPs are not part of this paper.
So far, it is mainly companion diagnostics that have made it into everyday healthcare: testing is currently prescribed or recommended for 98 active substances before the use of medication (as of 2022, vfa). However, diagnostics in personalized medicine go beyond these companion diagnostics.
Personalized medicine is unthinkable without targeted diagnostics
The topic of personalized medicine is primarily associated with pharmaceutical progress and drug innovations. Given the still large number of untreatable or insufficiently treatable diseases, this is hardly surprising.
However, the prerequisite for personalized medicine is targeted laboratory diagnostics. It enables an ever better understanding of physiological and pathological conditions. Suitable biomarkers are required for the respective clinical or therapeutic issue. The identification and validation of suitable biomarkers is seen by experts as a key driver for greater use of personalized medicine.
The areas of application are diverse
Diagnosis
Identifying the cause of the disease is a prerequisite for the right treatment. As in some cases the clinical symptoms do not allow a precise statement to be made about a known clinical picture, the use of biomarkers supports doctors in the diagnosis of many diseases.
Choosing the right therapy using predictive markers
Modern cancer therapies are now being developed using predictive diagnostics that can precisely identify the cancer-causing mutation and allow the appropriate therapy to be used in a targeted manner. This makes the efficient use of often expensive drugs feasible, as they are only used in patients who are most likely to respond to the drug. As a result, the failure rate decreases, but serious and even life-threatening side effects can also be minimized. In this way, biomarker-based tests provide the basis for choosing the right therapy. Such an approach is superior in every respect to the "trial and error" principle that is often still used today.
Monitoring during therapy
Therapies that extend over a longer period of time in particular can lose their effect or become ineffective. Here, too, personalized diagnostics can benefit patients. For example, the examination of anti-drug antibodies when using biologics in rheumatism patients helps to detect the loss of efficacy of expensive therapies and to switch to an effective medication or adjust the dosage in good time. Therapy monitoring using biomarkers gives patients the certainty that the therapy is working and thus improves adherence to therapy. Relapses and further irreversible progression of the disease can thus be prevented.
Prognostic markers
Prognostic markers can be used to obtain information about the course of the disease, e.g. the probability of relapse in the case of cancer. If minimal amounts of residual tumor material are detected in the blood after curative treatment, the risk of tumor recurrence increases. Imaging detection at this early stage after surgery is often unable to provide valid results.
Risk analysis for genetic predisposition
Cancers primarily occur at an older age. Only a small number of patients actually have a hereditary predisposition. Hereditary tumor syndromes usually occur in every family generation and the disease breaks out at a young age. A gene mutation is usually present. Known high-risk genes include BRCA1 and BRCA2. Patients with a mutation in one of these two genes have an increased risk of developing tumors compared to the general population. A familial risk due to hereditary predisposition can therefore be determined and closer monitoring can be carried out.
The right drug in the right dose for the right person
Continuous advances in imaging techniques, pathology and, in particular, molecular laboratory diagnostics are the value drivers of personalized medicine. They provide ever more specific information on patient characteristics and the disease itself. As a result, patients receive the most suitable medication for them. The prospect of successful treatment increases.
From an individual perspective, this means an increase in quality of life and an improvement in the outcome of treatment for patients. Ineffective yet burdensome drug therapies for non-responders (= non-response to a therapeutic measure) are avoided. Treatments that cannot be continued due to intolerances or that are unlikely to be effective but would expose the patient to the side effects of the therapy can also be avoided. A positive contribution is also made to dose optimization.
From a system perspective, personalized medicine means better quality of care in the form of faster diagnosis and more efficient use of resources. The reasons for this lie in particular in the avoidance of severe disease progression, serious side effects and the need for services such as hospital admissions and additional medication. The diagnostic test carried out before medication is administered - which is usually only required once - helps to save costs incurred over longer periods of time in other areas.
The VDGH is committed to the following
1) Further develop the reimbursement system
Advances in research findings in the field of personalized medicine mean that there are more and more areas of application for targeted diagnostics and therapy. It is therefore important to further develop the reimbursement system and make it future-proof. In Germany, the following applies: drugs are generally reimbursable by the SHI system once they have been approved. Associated companion diagnostics, on the other hand, require a number in the standardized assessment scale (EBM) after being placed on the market in order to be used in SHI-accredited medical care. In the past, there were long periods of time between the reimbursement of the medicinal product and the associated diagnostic. Legislators addressed this problem in 2017 with the SHI Drug Supply Strengthening Act and improvements were introduced. Since then, the evaluation committee must decide on an EBM code for the companion diagnostics until the Federal Joint Committee decides on the benefit assessment of the medicinal product (usually after six months). Despite these improvements, there is still a need for action in the following areas, which the legislator should address:
- → It is important for patients to be able to make use of companion diagnostics even in the time phase between the approval of the medicinal product and the decision of the evaluation committee. A provisional reimbursement option should therefore be created for this phase.
- Furthermore, the obligation of the evaluation committee to decide on an EBM code only applies if the companion diagnostics are mandatory. This regulation should also apply if the accompanying diagnostics are not mandatory, but are recommended according to the drug information (specialist information).
- In the inpatient system, remuneration is based on the so-called Diagnosis Related Groups (DRG). As a rule, these flat rates per case do not cover the costs of biomarker tests or do not cover the costs. In these cases, hospitals can initiate a so-called NUB procedure in order to receive (temporary) special fees for new examination and treatment methods. However, applications by hospitals for the refinancing of biomarkers have so far been unsuccessful without exception. Among other things, this can lead to seriously ill patients being referred to the outpatient sector for diagnostic purposes. As newly approved drugs are directly included in the OPS catalog (operation and procedure code) as a valued additional charge and initially financed via this, the associated accompanying diagnostic agent should always be included as an independent additional charge at the same time.
2) Grant the industry access to data
The use of data is of particular importance in personalized medicine. After all, it is not only the number of personalized approaches that is increasing, but also the complexity of diagnostics. The further development of personalized diagnostics requires suitable instruments and data access in order to systematically record and process medical information. Otherwise, there is a risk that important information from research (e.g. from treatment trials in top oncology centers such as the German Consortium for Translational Cancer Research) will not be available. Promising approaches include, for example, the Health Research Data Center or the model project for genome sequencing in accordance with Section 64e SGB V. Limitations exist here in that the very strict interpretation of data protection currently excludes the sharing of data between the centers and there are also limited access rights to data. The Health Data Utilization Act announced in the federal government's coalition agreement can provide a remedy here. It must be tackled promptly and should also allow industry access to health (care) data, naturally taking into account appropriate data protection. Other healthcare systems are clearly ahead of Germany in this respect.
3) Adapt clinical trials
Drug approval is a complex process in which the drug candidate goes through various clinical phases. The drug can only be launched on the market once these phases have been successfully completed. Evaluations of the drug are often carried out with the help of prospective randomized controlled trials (RCT). In the context of personalized medicine and the development of innovative diagnostics, this sole approach is not expedient, not least because the patient population is small. In this respect, retrospective studies of sample material from biobanks should also be taken into account to generate evidence in this area. Other European countries such as Denmark, Sweden or the UK also choose the route of direct funding of health economic studies by "state" institutes.
4) Expand research funding
In addition to existing funding opportunities, personalized medicine should be given a high priority in research policy. The focus should not only be on oncological diseases. Overall, support for translation is crucial to ensure that research findings on new therapeutic targets are also applied in healthcare. This supports small and medium-sized diagnostics companies in particular as drivers of innovation. Increased support for public-private partnerships and cooperation between academia and industry also makes sense.