Pharmaceutical Medicine is a medical discipline concerned with the discovery, evaluation, registration, monitoring, and clinical aspects of pharmaceutical development. All medical specialties overlap to some extent, and likewise, the boundaries of pharmaceutical medicine are elastic. But, at its center is the clinical testing of medicines, translation of pharmaceutical drug research into new medicines, safety and well-being of patients and research participants in clinical trials, and understanding the safety profile of medicines and their benefit-risk balance.
Pharmaceutical medicine is a listed medical specialty in the UK, Ireland, Switzerland, and Mexico. This official recognition is underlined by the availability of accredited education and training of specialist pharmaceutical physicians and the establishment and maintenance of standards of practice and professionalism in the competency, care, and conduct applied to their work and of growing public recognition and accountability. In the UK, the Faculty of Pharmaceutical Medicine of the Royal College of Physicians provides accreditation for the specialty.

Our institution enhances the knowledge, expertise, and skills of pharmaceutical physicians and other professionals involved in all scientific disciplines with regard to the discovery, development, research, and use of medicines worldwide, thus leading to the availability and appropriate use of safe and effective medicines for the benefit of patients and the society.

SR21 – Institute for Scientific Research act as a Contract Research Organization (CRO). We provide support to the pharmaceutical, biotechnology, and medical device industries in the form of research services outsourced on a contract basis. In general, a CRO may provide such services as biopharmaceutical development, biologic assay development, commercialization, preclinical research, clinical research, clinical trials management, and pharmacovigilance. Furthermore, CROs are designed to reduce costs for companies developing new medicines and drugs in niche markets. They aim to simplify entry into drug markets, and simplify development, as the need for large pharmaceutical companies to do everything ‘in-house’ is now redundant. CROs also support foundations, research institutions, and universities, in addition to governmental organizations. Many CROs specifically provide clinical study and clinical-trial support for drugs and/or medical devices. CROs range from large, international full-service organizations to small, niche specialty groups. CROs that specialize in clinical-trials services can offer their clients the expertise of moving a new drug or device from its conception to FDA/EMA marketing approval, without the drug sponsor having to maintain a staff for these services.
The International Council on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use, a 2015 Swiss NGO of pharmaceutical companies and others, defined a contract research organization (CRO), specifically pertaining to clinical trials services as: “A person or an organization (commercial, academic, or other) contracted by the sponsor to perform one or more of a sponsor’s trial-related duties and functions.”It further details the sponsor’s responsibilities in its good clinical practice guidelines:

– A sponsor may transfer any or all of the sponsor’s trial-related duties and functions to a CRO, but the ultimate responsibility for the quality and integrity of the trial data always resides with the sponsor. The CRO should implement quality assurance and quality control.
– Any trial-related duty and function that is transferred to and assumed by a CRO should be specified in writing. The sponsor should ensure oversight of any trial-related duties and functions carried out on its behalf, including trial-related duties and functions that are subcontracted to another party by the sponsor’s contracted CRO(s).
– Any trial-related duties and functions not specifically transferred to and assumed by a CRO are retained by the sponsor.
– All references to a sponsor in this guideline also apply to a CRO to the extent that a CRO has assumed the trial-related duties and functions of a sponsor.

Translational Medicine is a multi-faceted discipline, bridging the discovery, development, regulation, and utilization spectrum. It may include the application of research findings from genes, proteins, cells, tissues, organs, and animals, to clinical research in patient populations, all aimed at optimizing and predicting outcomes in specific patients. Developing treatments that take individual variability into account (“personalized medicine”) has given rise to this new discipline in science. Scientists in this fieldwork translate biological phenomena into targeted, evidence-based medicines that improve health and treat disease by more optimally matching drugs and individuals. Currently, at least 95 percent of pharmaceutical companies are performing translational research and the translational efforts are driving many of the new therapies entering the clinic today. For clinical pharmacology, the focus of translational research is on the discovery, development, regulation, and use of pharmacologic agents to improve clinical outcomes and inform optimal use of therapeutics in patients. In addition, translational research in clinical pharmacology may include the evaluation of various biomarkers of pharmacologic response and assessing the linkage between biomarker response and clinical endpoints in patients. Our broad description also includes how the response to therapeutic intervention in a particular disease may translate to a response in another disease, as well as the translation of safety signals across species and/or patient populations. Translational research is bolstered by a quantitative, model-based, and mechanistic understanding of disease biology and pharmacology. Consequently, core disciplines, including clinical pharmacology, pharmacogenomics, systems pharmacology, precision medicine, as well as others play an integral role in enabling translational research and translational medicine.
The most important challenge in health research is the process of turning observations in the laboratory, clinic, and community into interventions that improve the health of individuals and the public, from diagnostics and therapeutics to medical procedures and behavioral changes. Translational Science is the field of investigation focused on understanding the scientific and operational principles underlying each step of the translational process. For decades, translational science has faced the challenge of how to translate research findings into new effective medicines and technologies that rapidly deliver the medicines. This challenge has encouraged basic and translational sciences to work together towards this pivotal aim. Generations of scientists have struggled to make headway in de novo drug discovery. In principle, a strategy involving drug repurposing, in which a drug has already been tested and approved i.e. by the US FDA or the European EMA, can overcome the barriers of de novo drug discovery. However, the volume of approved or clinically failed drugs is large, emphasizing the difficulty of which drug to select that would be highly effective for the disease in question. The implementation of our strategic plan is guided by a broad and inclusive description of translational medicine to reflect the diversity of scientific disciplines involved in translational research within our society. For our department, translational research, translational science, and translational medicine are used interchangeably with a unifying principle that the ultimate purpose is to improve human health via a “bench to bedside” approach. The Institute for Scientific Research has taken a leading part in research-oriented, patient-oriented clinical treatments, in collaboration with designated patients’ medical teams. In that respect, our institution is studying drugs that are already approved to treat one disease or condition, to see if they are safe and effective for treating other diseases. Many agents approved for other uses already have been tested in humans, so detailed information is available on their pharmacology, formulation, and potential toxicity. Because drug repurposing builds upon previous research and development efforts, new candidate therapies could be ready for clinical trials quickly, speeding their review by the EMA / FDA and, if approved, their integration into health care. Discoveries about the molecular basis of disease provide unprecedented opportunities to translate research findings into new medicines. However, developing a brand-new drug takes an enormous amount of time, money, and effort, mainly due to bottlenecks in the therapeutic development process. Delays and barriers mean that translation of a promising molecule into an approved drug often takes more than 10 years. It is crucial to advance strategies to reduce this time frame, decrease costs and improve success rates.

Drug repurposing generally refers to studying drugs that are already approved to treat one disease or condition to see if they are safe and effective for treating other diseases. Many agents approved for other uses already have been tested in humans, so detailed information is available on their pharmacology, formulation and potential toxicity. Because repurposing builds upon previous research and development efforts, new candidate therapies could be ready for clinical trials quickly, speeding their review by the EMA / FDA and, if approved, their integration into health care.

Discoveries about the molecular basis of disease provide unprecedented opportunities to translate research findings into new medicines. However, developing a brand-new drug takes an enormous amount of time, money and effort, mainly due to bottlenecks in the therapeutic development process. Delays and barriers mean that translation of a promising molecule into an approved drug often takes more than 14 years. It is crucial to advance strategies to reduce this time frame, decrease costs and improve success rates.

Our Drug Repurposing research focuses on various disorders.

Selective references

Nosengo N. Can you teach old drugs new tricks? Nature. 2016;534:314–316.

Hay M, Thomas DW, Craighead JL, Economides C, Rosenthal J. Clinical development success rates for investigational drugs. Nat Biotechnol. 2014;32:40–51.

Wei Sun, Philip Sanderson, and Wei Zheng Drug combination therapy increases successful drug repositioning  10.1016/j.drudis.2016.05.015

Zhang H. Y., Tang X. C. Neuroprotective effects of huperzine A: new therapeutic targets for neurodegenerative disease. Trends in Pharmacological Sciences2006;27(12):619–625. doi: 10.1016/j.tips.2006.10.004.

Carley DW. Drug repurposing: identify, develop and commercialize new uses for existing or abandoned drugs. Part I. IDrugs. 2005;8(4):306–309.

Weir SJ, DeGennaro LJ, Austin CP. Repurposing approved and abandoned drugs for the treatment and prevention of cancer through public-private partnership. Cancer Res. 2012;72(5):1055–1058.

Thayer A. Drug repurposing. Chem Eng News. 2012;90:15–25.

Huang R, et al. The NCGC pharmaceutical collection: a comprehensive resource of clinically approved drugs enabling repurposing and chemical genomics. Sci Transl Med. 2011;3:80ps16–80ps16.

Drug development is the process of bringing a new pharmaceutical drug to the market once a lead compound has been identified through the process of drug discovery. It includes preclinical research, filing for regulatory status such as via the US Food and Drug Administration for an investigational new drug to initiate clinical trials on humans, and may include the step of obtaining regulatory approval with a new drug application to market the drug. The entire process, from concept through preclinical testing in the laboratory, to clinical trial development, including Phase I–III trials, to the approved vaccine or drug, typically takes more than a decade.

Preclinical Phase
New chemical entities (NCEs, also known as new molecular entities or NMEs) are compounds that emerge from the process of drug discovery. These have promising activity against a particular biological target that is important in disease. However, little is known about the safety, toxicity, pharmacokinetics, and metabolism of this NCE in humans. It is the function of drug development to assess all of these parameters prior to human clinical trials. A further major objective of drug development is to recommend the dose and schedule for the first use in a human clinical trial (“first-in-human” [FIH] or First Human Dose [FHD], previously also known as “first-in-man” [FIM]).
In addition, drug development must establish the physicochemical properties of the NCE: its chemical makeup, stability, and solubility. Manufacturers must optimize the process they use to make the chemical so they can scale up from a medicinal chemist producing milligrams, to manufacturing on the kilogram and ton scale. They further examine the product for suitability to package as capsules, tablets, aerosol, intramuscular injectable, subcutaneous injectable, or intravenous formulations. Together, these processes are known in preclinical and clinical development as chemistry, manufacturing, and control (CMC).
Many aspects of drug development focus on satisfying the regulatory requirements for a new drug application. These generally constitute a number of tests designed to determine the major toxicities of a novel compound prior to first use in humans. It is a legal requirement that an assessment of major organ toxicity be performed (effects on the heart and lungs, brain, kidney, liver and digestive system), as well as effects on other parts of the body that might be affected by the drug (e.g., the skin if the new drug is to be delivered on or through the skin). Such preliminary tests are made using in vitro methods (e.g., with isolated cells), but many tests can only use experimental animals to demonstrate the complex interplay of metabolism and drug exposure on toxicity.
The information is gathered from this preclinical testing, as well as information on CMC, and submitted to regulatory authorities (in the US, to the FDA), as an Investigational New Drug (IND) application. If the IND is approved, development moves to the clinical phase.

Clinical Phase
Clinical trials involve three or four steps:
Phase I trials, usually in healthy volunteers, determine safety and dosing.
Phase II trials are used to get an initial reading of efficacy and further explore safety in small numbers of patients having the disease targeted by the NCE.
Phase III trials are large, pivotal trials to determine safety and efficacy in sufficiently large numbers of patients with the targeted disease. If safety and efficacy are adequately proved, clinical testing may stop at this step and the NCE advances to the new drug application (NDA) stage.
Phase IV trials are post-approval trials that are sometimes a condition attached by the FDA, also called post-market surveillance studies.
The process of defining characteristics of the drug does not stop once an NCE is advanced into human clinical trials. In addition to the tests required to move a novel vaccine or antiviral drug into the clinic for the first time, manufacturers must ensure that any long-term or chronic toxicities are well-defined, including effects on systems not previously monitored (fertility, reproduction, immune system, among others).
If a vaccine candidate or antiviral compound emerges from these tests with acceptable toxicity and safety profile, and the manufacturer can further show it has the desired effect in clinical trials, then the NCE portfolio of evidence can be submitted for marketing approval in the various countries where the manufacturer plans to sell it. In the United States, this process is called a “new drug application”.
Most novel drug candidates (NCEs) fail during drug development, either because they have unacceptable toxicity or because they simply do not prove efficacy on the targeted disease, as shown in Phase II–III clinical trials. Critical reviews of drug development programs indicate that Phase II–III clinical trials fail due mainly to unknown toxic side effects (50% failure of Phase II cardiology trials), and because of inadequate financing, trial design weaknesses, or poor trial execution.
A study covering clinical research in the 1980–the 90s found that only 21.5% of drug candidates that started Phase I trials were eventually approved for marketing. During 2006–15, the success rate of obtaining approval from Phase I to successful Phase III trials was under 10% on average, and 16% specifically for vaccines. The high failure rates associated with pharmaceutical development are referred to as an “attrition rate”, requiring decisions during the early stages of drug development to “kill” projects early to avoid costly failures.

Cost of Drug Development
One 2010 study assessed both capitalized and out-of-pocket costs for bringing a single new drug to market as about US$1.8 billion and $870 million, respectively. A median cost estimate of 2015–16 trials for the development of 10 anti-cancer drugs was $648 million. In 2017, the median cost of a pivotal trial across all clinical indications was $19 million.
The average cost (2013 dollars) of each stage of clinical research was US$25 million for a Phase I safety study, $59 million for a Phase II randomized controlled efficacy study, and $255 million for a pivotal Phase III trial to demonstrate its equivalence or superiority to an existing approved drug, possibly as high as $345 million. The average cost of conducting a 2015–16 pivotal Phase III trial on an infectious disease drug candidate was $22 million.
The full cost of bringing a new drug (i.e., a new chemical entity) to market – from discovery through clinical trials to approval – is complex and controversial. In a 2016 review of 106 drug candidates assessed through clinical trials, the total capital expenditure for a manufacturer having a drug approved through successful Phase III trials was $2.6 billion (in 2013 dollars), an amount increasing at an annual rate of 8.5%. Over 2003–2013 for companies that approved 8–13 drugs, the cost per drug could rise to as high as $5.5 billion, due mainly to international geographic expansion for marketing and ongoing costs for Phase IV trials for continuous safety surveillance.
Alternatives to conventional drug development have the objective for universities, governments, and the pharmaceutical industry to collaborate and optimize resources.

Valuation
The nature of a drug development project is characterized by high attrition rates, large capital expenditures, and long timelines. This makes the valuation of such projects and companies a challenging task. Not all valuation methods can cope with these particularities. The most commonly used valuation methods are risk-adjusted net present value (rNPV), decision trees, real options, or comparables.
The most important value drivers are the cost of capital or discount rate that is used, phase attributes such as duration, success rates, and costs, and the forecasted sales, including the cost of goods and marketing and sales expenses. Less objective aspects like quality of the management or novelty of the technology should be reflected in the cash flows estimation.

Computing Initiatives
Novel initiatives include partnering between governmental organizations and industry, such as the European Innovative Medicines Initiative. The US Food and Drug Administration created the “Critical Path Initiative” to enhance innovation of drug development, and the Breakthrough Therapy designation to expedite the development and regulatory review of candidate drugs for which preliminary clinical evidence shows the drug candidate may substantially improve therapy for a serious disorder.
In March 2020, the United States Department of Energy, National Science Foundation, NASA, industry, and nine universities pooled resources to access supercomputers from IBM, combined with cloud computing resources from Hewlett Packard Enterprise, Amazon, Microsoft, and Google, for drug discovery. The COVID‑19 High-Performance Computing Consortium also aims to forecast disease spread, model possible vaccines, and screen thousands of chemical compounds to design a COVID‑19 vaccine or therapy. In May 2020, the OpenPandemics – COVID‑19 partnership between Scripps Research and IBM’s World Community Grid was launched. The partnership is a distributed computing project that “will automatically run a simulated experiment in the background [of connected home PCs] which will help predict the effectiveness of a particular chemical compound as a possible treatment for COVID‑19”.

Pharmacoeconomics refers to the scientific discipline that compares the value of one pharmaceutical drug or drug therapy to another. It is a sub-discipline of health economics. A pharmacoeconomic study evaluates the cost (expressed in monetary terms) and effects (expressed in terms of monetary value, efficacy, or enhanced quality of life) of a pharmaceutical product. Pharmacoeconomic studies serve to guide optimal healthcare resource allocation, in a standardized and scientifically grounded manner.
Pharmacoeconomics refers to the scientific discipline that compares the value of one pharmaceutical drug or drug therapy to another. It is a sub-discipline of health economics. A pharmacoeconomic study evaluates the cost (expressed in monetary terms) and effects (expressed in terms of monetary value, efficacy, or enhanced quality of life) of a pharmaceutical product. Pharmacoeconomic studies serve to guide optimal healthcare resource allocation, in a standardized and scientifically grounded manner.

Economic Evaluation
Pharmacoeconomics centers on the economic evaluation of pharmaceuticals and can use cost-minimization analysis, cost-benefit analysis, cost-effectiveness analysis or cost-utility analysis. Quality-adjusted life years have become the dominant outcome of interest in pharmacoeconomic evaluations, and many studies employ a cost-per-QALY analysis. Economic evaluations are carried out alongside randomized controlled trials and using methods of decision-analytic modeling. Pharmacoeconomics is a useful method of economic evaluation of various treatment options. As more expensive drugs are being developed and licensed it has become imperative especially in the context of developing countries where resources are scarce to apply the principles of pharmacoeconomics for various drugs and treatment options so that maximum improvement in quality of life can be achieved at minimum cost.

In Policy
In 1993, Australia became the first nation to use pharmacoeconomic analysis as part of the process for deciding whether new drugs should be subsidized by the Federal Government. The Pharmaceutical Benefits Advisory Committee (PBAC) advises Federal Government ministers on whether new drugs should be placed on a list of drugs that consumers can then purchase from pharmacies at a subsidized price. Since 1993, this approach to evaluating costs and benefits is used in Canada, Finland, New Zealand, Norway, Sweden, and the UK.

Impact of Pharmaceutical Innovations
Spending on new pharmaceuticals and R&D, although expensive, is considered to bring net benefits, as it decreases overall health care costs. A study of 30 countries estimated that 73% of the increase in life expectancy in recent decades is due to new pharmaceuticals alone. Another study found that new drugs have reduced hospital usage by 25% per decade by replacing more expensive forms of care like surgery. It has been estimated that the cost per additional life-year gained thanks to pharmaceutical innovation was US$2,730, compared with US$61,000 for dialysis, a commonly used benchmark.

The potential of molecular hydrogen (H2) for preventive and therapeutic applications.

H2 has been accepted to be an inert and nonfunctional molecule in our body. H2 reacts with strong oxidants such as hydroxyl radical in cells and proposes its potential for preventive and therapeutic applications. H2 has a number of advantages exhibiting extensive effects: H2 rapidly diffuses into tissues and cells, and it is mild enough neither to disturb metabolic redox reactions nor to affect signalling reactive oxygen species; therefore, there should be no or little adverse effects of H2.
The numerous publications on its biological and medical benefits revealed that H2 reduces oxidative stress not only by direct reactions with strong oxidants, but also indirectly by regulating various gene expressions. Moreover, by regulating the gene expressions, H2 functions as an anti-inflammatory and anti-apoptotic, and stimulates energy metabolism. In addition to growing evidence obtained by model animal experiments, extensive clinical examinations were performed or are under investigation. Since most drugs specifically act to their targets, H2 seems to differ from conventional pharmaceutical drugs. Owing to its great efficacy and lack of adverse effects, H2 has promising potential for clinical use against many diseases.

Our H2 research focuses on 3 areas: Metabolic syndrome, Neurocognitive disorders (NCDs), other Neurodegenerative disorders, Cancers.

Selective references

Kikkawa YS, Nakagawa T, Horie RT, Ito J. Hydrogen protects auditory hair cells from free radicals. Neuroreport. 2009;20:689–94.

Wallace DC. A mitochondrial paradigm of metabolic and degenerative diseases, aging, and cancer: a dawn for evolutionary medicine. Annu Rev Genet. 2005;39:359–407

Salganik RI. The benefits and hazards of antioxidants: controlling apoptosis and other protective mechanisms in cancer patients and the human population. J. Am. Coll. Nutr. 2001;20:464S–72S.

Kawasaki H, Guan J, Tamama K. Hydrogen gas treatment prolongs replicative lifespan of bone marrow multipotential stromal cells in vitro while preserving differentiation and paracrine potentials. Biochem Biophys Res Commun. 2010;397:608–13.

Andersen JK. Oxidative stress in neurodegeneration: cause or consequence? Nat Med. 2004;10(Suppl):S18–25

Ohta S, Ohsawa I. Dysfunction of mitochondria and oxidative stress in the pathogenesis of Alzheimer’s disease: on defects in the cytochrome c oxidase complex and aldehyde detoxification. J Alzheimers Dis. 2006;9:155–66

Brambilla D, Mancuso C, Scuderi MR, et al. The role of antioxidant supplement in immune system, neoplastic, and neurodegenerative disorders: a point of view for an assessment of the risk/benefit profile. Nutr J. 2008;7:29.

Cross AH, Tuohy VK, Raine CS. Development of reactivity to new myelin antigens during chronic relapsing autoimmune demyelination. Cell Immunol 1993; 146(2):261–269.

Heat-shock proteins (HSPs), or stress proteins, are highly conserved and present in all organisms and in all cells of all organisms. Selected HSPs, also known as chaperones, play crucial roles in folding/unfolding of proteins, assembly of multiprotein complexes, transport/sorting of proteins into correct subcellular compartments, cell-cycle control and signalling, and protection of cells against stress/apoptosis. More recently, HSPs have been implicated in antigen presentation with the role of chaperoning and transferring antigenic peptides to the class I and class II molecules of the major histocompatibility complexes. In addition, extracellular HSPs can stimulate professional antigen-presenting cells of the immune system, such as macrophages and dendritic cells. HSPs constitute a large family of proteins that are often classified based on their molecular weight: hsp10, hsp40, hsp60, hsp70, hsp90, etc.

Our HSPs research focuses on 2 areas: Neurocognitive disorders (NCDs), other Neurodegenerative disorders, Cancers.

Selected references

Jaattela M. Heat shock proteins as cellular lifeguards. Ann. Med. 1999;31:261–271. doi: 10.3109/07853899908995889.

Jego G., Hazoume A., Seigneuric R., Garrido C. Targeting heat shock proteins in cancer. Cancer Lett. 2013;332:275–285. doi: 10.1016/j.canlet.2010.10.014.

Macario A.J., Conway de Macario E. Molecular chaperones: Multiple functions pathologies and potential applications. Front. Biosci. A J. Virtual Libr. 2007;12:2588–2600. doi: 10.2741/2257.

Heat shock proteins in neurodegenerative diseases: pathogenic roles and therapeutic implications.
Adachi H1, Katsuno M, Waza M, Minamiyama M, Tanaka F, Sobue G. DOI: 10.3109/02656730903315823

Jolly C., Morimoto R.I. Role of the heat shock response and molecular chaperones in oncogenesis and cell death. J. Natl. Cancer Inst. 2000;92:1564–1572. doi: 10.1093/jnci/92.19.1564.

Ciocca D.R., Calderwood S.K. Heat shock proteins in cancer: Diagnostic, prognostic, predictive, and treatment implications. Cell Stress Chaperones. 2005;10:86–103. doi: 10.1379/CSC-99r.1.

Aridon P, Geraci F, Turturici G, D’Amelio M, Savettieri G, Sconzo G. Protective role of heat shock proteins in Parkinson’s disease. Neurodegener Dis. 2011;8:155–68.

Cohen IR. Autoimmunity to chaperonins in the pathogenesis of arthritis and diabetes. Annu Rev Immunol 1991; 9:567–589.

Start typing and press Enter to search