Medical research (or biomedical research), also known as experimental medicine, encompasses a wide range of research, ranging from “basic research” (also known as bench science or bench research), which involves fundamental scientific principles that may apply to a preclinical understanding, to clinical research, which involves studies of people who may be clinical trial subjects. This spectrum includes applied research, also known as translational research, which is done to further medical understanding.
In the pharmaceutical industry’s drug development pipelines, both clinical and preclinical research stages occur, with the clinical phase signified by the phrase clinical trial. However, only a portion of clinical or preclinical research is focused on a single pharmacological goal. Pharmaceutical research is just a minor component of medical research due to the need for basic and mechanism-based knowledge, diagnostics, medical technologies, and non-pharmaceutical therapy.
The increasing lifespan of humans over the last century may be credited in large part to medical research discoveries. Vaccines for measles and polio, insulin treatment for diabetes, classes of antibiotics for treating a variety of ailments, medication for high blood pressure, improved treatments for AIDS, statins and other treatments for atherosclerosis, new surgical techniques such as microsurgery, and increasingly successful cancer treatments are among the major benefits of medical research. The Human Genome Project is intended to bring in new, helpful testing and therapies. However, many difficulties persist, including the emergence of antibiotic resistance and the obesity pandemic.
The majority of research in the subject is conducted by biomedical scientists, although other types of biologists make substantial contributions. Medical research on people must closely adhere to the medical ethics sanctioned in the Helsinki Declaration and the hospital review board where the study is done. Research ethics are expected in all instances.
Medical research phases
Fundamental medical research
Cellular and molecular biology, medical genetics, immunology, neurology, and psychology are some examples of fundamental medical study. Researchers, mostly at universities or government-funded research organisations, seek to understand the cellular, molecular, and physiological processes underlying human health and illness.
Pre-clinical research focuses on understanding processes that may lead to human clinical trials. Typically, no ethical permission is required, the activity is overseen by scientists rather than doctors, and it is carried out at a university or firm rather than a hospital.
People are used as experimental subjects in clinical research. It is usually overseen by doctors and carried out by nurses in a medical context, such as a hospital or research clinic, and it needs ethical permission.
Many nations get research support via research agencies and private organisations, which give funds for equipment, wages, and research expenditures. The United States, Europe, Asia, Canada, and Australia spent $265.0 billion in 2011, a 3.5% increase from $208.8 billion in 2004. In 2011, the United States supplied 49% of federal funding from these areas, down from 57% in 2004.
Funding organisations in the United Kingdom, such as the National Institute for Health and Care Research (NIHR) and the Medical Research Council, are funded by UK taxpayers and transfer profits to institutions via competitive research grants. The Wellcome Trust is the UK’s biggest non-governmental source of money for biomedical research, providing over £600 million in grants to scientists and funding for research institutions each year.
In the United States, figures from the National Science Foundation’s (NSF) regular surveys reveal that government agencies contributed just 44% of the $86 billion spent on fundamental research in 2015. The National Institutes of Health and pharmaceutical corporations provide $26.4 billion and $27 billion, respectively, accounting for 28% and 29% of the total.
Biotechnology businesses ($17.9 billion, 19% of total), medical device companies ($9.2 billion, 10% of total), other federal sources, and state and municipal governments are also important donors. About 3% of the financing came from foundations and charities, headed by the Bill and Melinda Gates Foundation. These donors are seeking to maximise their return on public health investment. To maximise the return on investment in medicine, one option recommended is to subsidise the creation of open source hardware for medical research and therapy.
The passage of orphan drug laws in several countries has expanded financing available for the development of therapies to treat uncommon diseases, leading in discoveries that were previously uneconomical to pursue.
Biomedical research supported by the government
Since the National Institutes of Health (NIH) was established in the mid-1940s as the primary source of U.S. government support for biomedical research, investment objectives and budget levels have changed. NIH financing for biomedical research grew from 11 billion to 27 billion between 1995 and 2010. Despite the rise in government investment, breakthroughs measured by citations to publications and the number of medications approved by the FDA remained unchanged during the same time period. According to financial predictions, government expenditure will stay unchanged in the foreseeable future.
Trends in government spending in the United States
The National Institutes of Health (NIH) is the body in charge of managing the vast majority of government funding for scientific research. It supports around 280 health-related initiatives. There have been two noteworthy periods of NIH assistance throughout the last century. From 1995 to 1996, funding jumped from $8.877 billion to $9.366 billion, marking the beginning of what is known as the “doubling period” of fast NIH financing. The second important phase began in 1997 and concluded in 2010, when the NIH began to organize research expenditures in order to connect with the scientific community.
Biomedical research supported privately (by industry)
Since 1980, industrial financing for biomedical research has increased from 32% to 62%, resulting in the creation of several life-saving medical discoveries. In the United States, the relationship between corporate and government-funded research has shifted dramatically throughout the years. Congress approved the Bayh-Dole Act in 1980 to encourage a more positive interaction between government and industry-funded biomedical research. The Bayh Doyle Act let private firms to seek for government-funded funds for biomedical research, allowing the corporations to licence the technology. Between 1994 and 2003, both government and industry research spending expanded fast; industry enjoyed a compound annual growth rate of 8.1% each year and only slightly decreased to a compound annual growth rate of 5.8% from 2003 to 2008.
In the realm of medical research, a “conflict of interest” has been described as “a set of conditions in which professional judgement concerning a primary interest (such as a person’s welfare or the validity of research) tends to be unduly influenced by a secondary interest (such as financial gain).”
Since Samuel Hopkins Adams’ pronouncement, there have been significant improvements in the regulation of industry-funded biomedical research. The Pure Food and Drugs Act of 1906 was approved by Congress in 1906. The Shirley Amendment was introduced by Congress in 1912 to ban the widespread broadcast of misleading information about drugs. The Food and Drug Administration was originally established in 1930 by the McNarey Mapes Amendment to supervise food and drug regulation in the United States. The Kefauver-Harris Amendments to the Food, Drug, and Cosmetics Act of 1962 mandated that before a drug could be sold in the United States, the FDA must first certify that it was safe. The Kefauver-Harris amendments also required more thorough clinical testing before a medicine could be released to the market. The Kefauver-Harris amendments were received with hostility from industry owing to the necessity of longer clinical trial durations, which would shorten the time it takes for an investor to get a return on their investment. Patents in the pharmaceutical business are normally awarded for a duration of 20 years, and most patent applications are filed during the early phases of product development. According to Ariel Katz, it takes an extra 8 years after a patent application is received before the FDA authorises a medicine for commercialization. As a result, a corporation would only have 12 years to sell the medicine before seeing a return on their investment.
Following the 1962 Kefauver-Harris amendments, which resulted in a steep reduction in the number of new pharmaceuticals entering the US market, economist Sam Petlzman found that the cost of lost innovation was larger than the savings realised by consumers who no longer purchased useless drugs. Congress approved the Hatch-Waxman Act, often known as the Drug Price Competition and Patent Term Restoration Act of 1984, in 1984. The Hatch-Waxman Act was enacted with the intention of creating stronger incentives for innovation and private sector financing for investment by allowing brand manufacturers to prolong their patent for an extra 5 years.
The industry-funded biomedical research relationship is one in which industry finances academic institutions, which then hire scientific investigators to do research. A concern that occurs with an industry-funded initiative is that corporations may choose to ignore notifying the public of detrimental consequences in order to better advertise their product. Following the 2003 publication of “Scope and Impact of Financial Conflicts of Interest in Biomedical Research” in The Journal of American Association of Medicine, a list of studies shows that public fear of conflicts of interest that exist when biomedical research is funded by industry can be considered valid. This article comprised 37 papers that satisfied certain criteria for determining whether or not an academic institution or scientific investigator supported by industry participated in behaviour that may be interpreted as a conflict of interest in the area of biomedical research.
According to the findings of one study, 43% of scientific investigators employed by a participating academic institution received research-related gifts and discretionary expenditures from industrial sponsors. Another poll of participants revealed that 7.6% of investigators were financially connected to study sponsors, including paid speaking engagements (34%), consultancy agreements (33%), advisory board seats (32%), and stock (14%). According to a 1994 survey, 58% of 210 life science businesses claimed that scientists were obliged to suppress information about their research in order to lengthen the life of the interested companies’ patents. Experts in the area of biomedical research are studying conflict of interest declaration rules and laws in order to minimise conflicts of interest that may impact the results of biomedical research.
Two statutes that are still in place, one approved in 2006 and the other in 2010, were essential in establishing funding reporting criteria for biomedical research and outlining hitherto unrequired reporting rules. The Federal Funding Accountability and Transparency Act of 2006 requires all organisations receiving more than $25,000 in federal dollars to submit yearly expenditure reports, which include disclosure of executive salaries. The statute was amended in 2010 to require progress reports to be filed alongside financial reports. On usaspending.gov, data from the federal requirement is handled and made publicly accessible. Other reporting mechanisms exist in addition to the main source, usaspending.gov: data on biomedical research funding from federal sources is made publicly available by the National Health Expenditure Accounts (NHEA), data on health services research, which accounts for approximately 0.1% of federal funding on biomedical research, is available through the Coalition of Health Services Research, the Agency for Healthcare Research and Quality, and the Centres for Disease Control and Prevention.
There are currently no funding reporting requirements for industry-sponsored research, although there has been some voluntary progress towards this aim. Major pharmaceutical stakeholders such as Roche and Johnson & Johnson made financial information publicly available in 2014, and the Pharmaceutical Research and Manufacturers of America (PhRMA), the most prominent professional association for biomedical research companies, has recently begun to provide limited public funding reports.
Other areas range from the ancient to the twentieth century.
The Book of Daniel has the first account of a medical trial, in which Babylonian king Nebuchadnezzar ordered royal blood youths to consume only red meat and wine for three years, while another set of youths ate only beans and water. The goal of the experiment was to see whether a diet of vegetables and water was healthier than a diet of wine and red meat. At the conclusion of the experiment, the study met its goal: the kids who ate just beans and water were notably healthier. Scientific interest about health outcomes from various therapies has existed for centuries, but it wasn’t until the mid-nineteenth century that an organisational structure was built to encourage and govern this research. Vannevar Bush stated in 1945 that biomedical scientific research was “the pacemaker of technological progress,” an idea that contributed to the initiative to establish the National Institutes of Health (NIH) in 1948, a historical milestone that marked the beginning of a near-century significant investment in biomedical research.
The twentieth and twenty-first centuries in the United States
To date, the NIH has provided more financial assistance for medical research than any other organisation in the world, and it is credited with countless inventions that have benefited worldwide health. The financing of biomedical research has changed dramatically during the last century. In the early years of the NIH, innovations such as the polio vaccine, antibiotics, and antipsychotic drugs led to societal and political support for the institution. Political actions in the early 1990s result in a doubling of NIH funding, ushering in an age of rapid scientific advancement. Since the beginning of the century, there have been tremendous changes in the period; approximately about the turn of the century, the cost of trials drastically rose but the rate of scientific discoveries did not keep pace.
Biomedical research investment rose much faster than GDP growth in the United States during the last decade: between 2003 and 2007, spending climbed 14% per year, while GDP growth increased 1% (both measurements adjusted for inflation). Industry, non-profit organisations, state and federal financing all contributed to an increase in funding from $75.5 billion in 2003 to $101.1 billion in 2007. Biomedical research investment fell 2% in real terms in 2008 due to the urgency of government funding priorities and stagnating business spending during the crisis.
Despite an increase in total funding in biomedical research, the number of medication and device approvals has stagnated, with certain fields seeing a significant reduction over the same time span.
In 2010, industry supported research accounted for 58% of expenditures, NIH for 27%, state governments for 5%, non-NIH-federal sources for 5%, and not-for-profit organisations accounted for 4% of funding. From 2003 to 2007, federally supported biomedical research expenditures grew nominally by 0.7% (adjusted for inflation). Previous studies revealed a significant disparity in government spending, with federal money increasing 100% (adjusted for inflation) from 1994 to 2003.
Over 85% of government biomedical research expenditures are managed by the NIH. NIH funding for biomedical research fell from $31.8 billion in 2003 to $29.0 billion in 2007, representing a 25% fall (in real terms adjusted for inflation), whereas non-NIH federal spending enabled the government to maintain its financial support levels during the decade (a 0.7% four-year rise). Spending on industry-initiated research grew by 25% (adjusted for inflation) between 2003 and 2007, rising from $40 billion in 2003 to $58.6 billion in 2007. Between 1994 and 2003, industry-sourced spending climbed by 8.1%, a dramatic contrast to the 25% growth in recent years.
Pharmaceutical company expenditure was the largest contributor to total industry sponsored biomedical research spending, although it only climbed 15% (adjusted for inflation) from 2003 to 2007, while device and biotechnology businesses accounted for the bulk of investment. Stock performance, which may be an indicator of future business growth or technological direction, has improved significantly for both medical device and biotechnology firms. Less stringent FDA clearance procedures for devices as compared to medications, reduced trial costs, lower product price and profitability, and predictable effect of new technology owing to a limited number of rivals are regarded to be contributing causes to this increase. Another noticeable shift during the era was a shift in emphasis to late-stage research trials; previously dispersed, since 1994, an increasingly large portion of industry-sponsored research has been late phase trials rather than early-experimental phases, now accounting for the majority of industry sponsored research. This trend may be attributed to lower-risk investment and a quicker development-to-market timeline. The low risk preference is also reflected in the trend of large pharmaceutical firms acquiring smaller companies that hold patents to newly developed drug or device discoveries that have not yet been approved by the FDA (large companies are mitigating their risk by purchasing technology created by smaller companies in early-phase high-risk studies). Medical research funding from universities climbed 7.8% (adjusted for inflation) from $22 billion in 2003 to $27.7 billion in 2007. The most highly financed institutions got 20% of HIN medical research funding in 2007, while the top 50 institutions received 58% of NIH medical research funding. The percentage of money awarded to the biggest universities has grown just marginally since 1994. In comparison to government and private financing, health policy and service research accounted for a little portion of sponsored research; $1.8 billion was allocated to health policy and service research in 2003, rising to $2.2 billion in 2008.
The US government’s stagnant investment rates over the last decade may be attributed in part to the field’s problems. To far, only two-thirds of published drug trial findings have reproducible outcomes, which raises issues from a regulatory viewpoint in the United States, where significant investment has been made on research ethics and standards, yet trial results remain inconsistent. A spokesman for the National Institute of Neurological Disorders and Stroke, an NIH agency, stated that there is “widespread poor reporting of experimental design in articles and grant applications, that animal research should follow a core set of research parameters, and that a concerted effort by all stakeholders is needed to disseminate best reporting practises and put them into practise.”
Regulations and policies
Medical research is strictly regulated. Most nations establish national regulatory agencies to regulate and monitor medical research, such as the creation and marketing of new pharmaceuticals. The Food and medication Administration regulates new medication development in the United States; the European Medicines Agency (also known as EudraLex) in Europe; and the Ministry of Health, Labour, and Welfare in Japan. The World Medical Association establishes ethical guidelines for medical practitioners engaged in medical research. The Declaration of Helsinki is the most basic of them all. The International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH) develops regulations and recommendations for the development of new medications, such as the Good Clinical Practise (GCP) guidelines. All regulatory concepts are founded on a country’s ethical standards code. This is why therapy for one illness may be prohibited in one nation but permitted in another.
Vulnerabilities and flaws
The hypercompetition for the resources and jobs necessary to perform science seems to be a fundamental fault and risk in biomedical research. The rivalry seems to stifle the creativity, collaboration, risk-taking, and unique thought necessary to achieve significant discoveries. Other consequences of today’s highly competitive research environment appear to be a large number of research publications whose findings cannot be replicated, as well as perverse incentives in research funding that encourage grantee institutions to grow without investing adequately in their own faculty and facilities. Other concerning trends include a decrease in the proportion of significant research funds going to younger scientists and a consistent increase in the age at which investigators obtain their first financing.
Medical remedies are often commercialised by private enterprises such as pharmaceutical corporations or medical device companies after clinical study. According to one estimate, one-third of Medicare physician and outpatient hospital expenditure in 2011 was on new technology that were not accessible in the previous decade.
Because medical treatments are always being explored, the distinction between experimental and standard of care medicines is not always apparent, especially when cost-effectiveness is taken into account. Payers have utilisation management clinical guidelines that state that “experimental or investigational” therapies will not be reimbursed, or that the therapy must be medically required or superior to less expensive treatments. Proton treatment, for example, was authorised by the FDA, but private health insurance in the United States deemed it untested or unneeded due to its high cost, even if it was eventually reimbursed for select tumours.
Subjects of study
Biomedical research includes the following areas:
- Psychological health
- Molecular biology
- Biology at the molecular level
- Medicine for prevention
- The state of public health
- Tissue engineering
- Palliative care medicine