companion diagnostic assignment on strategies to select diagnostic tools

Question

Task: How can health can facilities use companion diagnostic assignment research methodologies to determine the most effective diagnostic tools to use at their facility?

Answer

Introduction
Thiscompanion diagnostic assignment explores strategies healthcare facilities can select the best diagnostic tools. A companion diagnostic refers to a medical device in vitro device which facilitates information which is vital for the effective and safe use of a corresponding biological or drug product. A companion diagnostic test allows healthcare professionals to determine whether a specific therapeutic product's advantage to patients will outweigh any probable serious risks or side effects. This test can identify patients that are most likely to benefit from a specific therapeutic product or have serious side effects as a consequence of treatment. The purpose of this companion diagnostic assignment is to investigate the development of a companion biomarker for SCN5A.

Background
The SCN5A gene cyphers the alpha subunit of the central cardiac sodium channel Nav1.5 which is known to be accountable for maintaining the normal functioning of inward sodium current (Ina). Genetic variants of SCN5A are encompassed in a number of inherent cardiac channelopathies such as long QT syndrome, Brugada syndrome (BrS) and cardiac conduction system dysfunction. At the same time, SCN5A variants are also prevalent to be correlated with dilated cardiomyopathy, myocardial contractile dysfunction and heart failure(Li et al., 2018). The purpose of this companion diagnostic assignment is to suggest a strategy for the co-development of a companion diagnostic along with the drug treatment rather than the alternative strategy of developing a biomarker test after the approval of the drug.

Issues
Co-development of biomarkers and drugs must be considered when the biomarker is complicatedly associated with the use of the drug. There are certain benefits and risks to co-development and it is imperative to address and consider the same during the initiation of the process. Some of the challenges in attaining successful biomarker programs identified on this companion diagnostic assignment include the clinical specificity and sensitivity of biomarkers safety, and the implementation to the clinical level due to issues such as proof-of-concept and accurate data acquisition(Zafarullah, 2020).

companion diagnostic assignment Literature Review
According to Mankoff et al. (2016), the goal of targeted and individualised treatment and precision medicine needs the assessment of probable therapeutic targets to direct the selection of treatment. Companion diagnostics often termed biomarkers are used to direct precision medicine for highly targeted drugs which have thus far been almost based on in vitro assay of biopsy material. One of the closely associated capabilities to assess the impact of the drug on the underlying and target disease process is to determine whether the chosen therapy is likely to be successful and effective. Biomarkers which are targeted specifically are known as companion diagnostics and it tends to measure the therapeutic target closely associated with partner molecules or itself. On the other hand, biomarkers which are used to assess the impact of the treatment on the process of the disease is known as a response biomarker.

A companion diagnostic assignment study by Seo& Strong (2021) states that the optimisation of the treatment tactics has become possible on the evidence facilitated by biomarkers prior to the administration of treatments. These advances have raised expectations of treatments that are guided biomarker therapies due to their potential of improving patient outcomes and attainment of efficient allocation of resources in healthcare. This study has tested an intervention strategy of biomarker-guided therapies by companion diagnostics wherein patients were tested before the administration of targeted therapies in accordance with their biomarker status. The study further demonstrated that the model structure of data requirements and strategy comparisons relevant to the characteristics of companion biomarker testing which needed incorporation into the health modelling of biomarker targeted therapies wherein those wanting structural changes can replicate the processes through the creation of transition matrices through modifications.

As per the companion diagnostic assignment paper by Huber et al. (2021) precision, medicine facilitates a promising vision for the development of new targeted drugs, especially in areas with the high medical requirement. It is assumed that drugs tend to react differently amongst different patients and precision medicine is in the requirement of relevant interaction between treatment and patients resulting in improved tolerability and efficacy in a given subgroup of patients. In contrast to the massive expectations in precision medicine, the utility of biomarker-based selection of patients in regards to clinical outcomes is substantiated by expectations and clinical data might be too optimistic. Successful approval of drugs usually calls for a demonstration of the tolerability and effectiveness in the biomarker-defined subgroup which does not need to be evidence of the usefulness of the restriction to a specified population. The balance between benefit and risk to the biomarker-negative population primarily depends on the degree of the biological plausibility of the biomarker in regards to predicting a given medicine is another important factors observed on this companion diagnostic assignment.

According to Watson et al. (2021), while significant device-based and pharmacological advances have been made in heart failure, successful strategies for preserved ejection fraction stay elusive. Kott et al. (2022) state biomarker studies in cardiac diseases have used dichotomous outcomes such as if the patient had a myocardial infarction, whether they have died or not and had heart failure or not. Prior reports of blood-based biomarkers stated success in facilitating usefulness for cardiovascular disease and were aimed to improve the diagnosis of acute coronary syndrome and myocardial infarction.

companion diagnostic assignment Data Collection
For the purpose of this companion diagnostic assignment, secondary data has been extracted on the chosen topic. Secondary data refers to the data which has already been published or collected by someone for specific purposes(Kabir, 2016). Some of the main sources of data for this research were published journal articles from credible websites such as ResearchGate, Seminars in Nuclear Medicine, Frontiers in Physiology and PubMed. The exclusion/inclusion criteria for the research were in terms of language wherein English language was selected, availability of full texts wherein data which had full access were chosen and time period wherein data were selected from the year 2014 to upkeep relevance.

Discussion of Different Options
When deciding the ways to use biomarkers in programs of drug development there are three main sources of biomarker evidence which can be considered by the FDA to pervade regulatory decisions. The three pathways identified on this companion diagnostic assignment are a specific drug approval and development process, scientific community consensus and CDER’s Biomarker Qualification Program. Cardiac biomarkers have been emerging as a novel strategy for the treatment and management of patients with heart failure. There are two crucial characteristics which successful biomarkers for guiding heart therapy will hold firstly, it is crucial for useful biomarkers to reflect the severity of the heart failure of pathophysiology. An effective marker must guide therapies while accurately predicting potential risks. Secondly, effective biomarkers for guiding therapy must amplify the proper application of therapies that are evidence-based for heart failures(Pruett et al., 2014).

Recommendations
The development of CDx or companion diagnostic is a sturdy tool in precision medicine and it typically follows one of the three pathways: bridging, co-development and follow-on. It is crucial to screen target patients and identify drug targets accurately which works towards reducing cycle times and development costs for pharmaceutical companies. Data generated from FDA displays that 25% (11 out of 44) of therapeutic medical product approvals in the year 2019 considered personalised medicines and personalised medicines amplified from 21% in the year 2014 to 42% in the year 2018(Sheng, 2020).

Underlining the complexity and challenges in developing intertwined products the draft guidance of the FDA recommends that organisations develop them in tandem since the agency supports parallel approval as it cannot hasten approval. The guidance states that the general principles to guide the co-development of therapies and companion diagnostics, considerations must be made for planning clinical trials and sponsors must be wary of the regulatory requirements. In in vitro companion diagnostics, it is crucial to identify how patients will most likely benefit from a drug, how patients can be at an increased risk for the results of a drug, and monitor the response to treatment with the aim of adjusting and identifying the population of patients for whom therapy has been appropriately studied and found to be effective and safe(FDA News, 2016).

As stated by Samy (2016) CDx led drug development can minimise the costs of clinical trials by up to 60% and these cost savings are dependent on the capability of CDx-guided drug candidates in displaying greater efficacy at the time of clinical trials with minimum population. Companion diagnostics recognise the subset of patients with a higher likelihood to respond to therapies prior to administering and narrowing trial sizes substantially. Apart from that CDx led drug development not only amplifies the efficacy of therapies but also consequences in more desirable profiles of safety and more drug approvals. The companion diagnostic assignment research shows these tests facilitate drug developers to choose prime candidates for a specific therapy while eliminating the noise in the evidence by weeding out profiles of patients with high-risk effects.

Conclusion
The cost savings facilitated by CDx are especially crucial since CDx filters outpatients that are unlikely to respond to a specific treatment which shrinks the addressable patient population for the chosen therapy. The overall assessment has worked towards evaluating a strategy of co-development of companion diagnostic along with drug treatment for SCN5A. The companion diagnostic assignment has analysed current literature on the topic of companion diagnostics and narrowed down a discussion of different options which can be undertaken to attain the same. Based on the discussion the report has provided recommendations for attaining companion diagnostic with drug development.

References
FDA News. (2016). Guidance Covers Co-development of Companion Diagnostics, Drugs | 2016-08-12 | FDANews | FDAnews.companion diagnostic assignment Www.fdanews.com. https://www.fdanews.com/articles/177974-guidance-covers-co-development-of-companion-diagnostics-drugs
Huber, C., Friede, T., Stingl, J., & Benda, N. (2021). Classification of Companion Diagnostics: A New Framework for Biomarker-Driven Patient Selection. Therapeutic Innovation & Regulatory Science, 56(2), 244–254. https://doi.org/10.1007/s43441-021-00352-2
Kabir, S. M. S. (2016, July). Methods Of Data Collection. ResearchGate. https://www.researchgate.net/publication/325846997_METHODS_OF_DATA_COLLECTIONcompanion diagnostic assignment
Kott, K. A., Bishop, M., Yang, C. H. J., Plasto, T. M., Cheng, D. C., Kaplan, A. I., Cullen, L., Celermajer, D. S., Meikle, P. J., Vernon, S. T., & Figtree, G. A. (2022). Biomarker Development in Cardiology: Reviewing the Past to Inform the Future. Cells, 11(3), 588. https://doi.org/10.3390/cells11030588
Li, W., Yin, L., Shen, C., Hu, K., Ge, J., & Sun, A. (2018). SCN5A Variants: Association With Cardiac Disorders. Frontiers in Physiology, 9. https://doi.org/10.3389/fphys.2018.01372
Mankoff, D. A., Edmonds, C. E., Farwell, M. D., & Pryma, D. A. (2016). Development of Companion Diagnostics. Seminars in Nuclear Medicine, companion diagnostic assignment46(1), 47–56. https://doi.org/10.1053/j.semnuclmed.2015.09.002
Pruett, A., Lee, A., Patterson, J., Schwartz, T., Glotzer, J., & Adams, K. (2014). Evolution of Biomarker Guided Therapy for Heart Failure: Current Concepts and Trial Evidence. Current Cardiology Reviews, 11(1), 80–89.
https://doi.org/10.2174/1573403x09666131117123525
Samy, M. (2016, August 25). Companion Diagnostics (CDx): More Drugs at a Fraction of the Cost. ARK Invest. https://ark-invest.com/articles/analyst-research/companion-diagnostics-cdx/
Seo, M. K., & Strong, M. (2021). A Practical Guide to Modeling and Conducting a Cost-Effectiveness Analysis of Companion Biomarker Tests for Targeted Therapies Using R: Tutorial Paper. PharmacoEconomics, 39(12), 1373–1381. https://doi.org/10.1007/s40273-021-01069-8companion diagnostic assignment
Sheng, J. (2020, December 1). Driving Co-Development of Therapeutic Drugs and Companion Diagnostics. DIA Global Forum. https://globalforum.diaglobal.org/issue/december-2020/driving-co-development-of-therapeutic-drugs-and-companion-diagnostics/
Watson, C. J., Gallagher, J., Wilkinson, M., Russell-Hallinan, A., Tea, I., James, S., O’Reilly, J., O’Connell, E., Zhou, S., Ledwidge, M., & McDonald, K. (2021). Biomarker profiling for risk of future heart failure (HFpEF) development. Journal of Translational Medicine, 19(1). https://doi.org/10.1186/s12967-021-02735-3
Zafarullah, M. (2020, July 16). Biomarker Development: A Tool to Prevent Neurodegenerative Disorders. UC Davis Biotechnology Program. https://biotech.ucdavis.edu/news/
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