What is Standard of Care in clinical trials?
Clinical trials aim to test the efficacy and safety of a new investigational medicinal product (IMP). This is done by conducting trials that study the effects of the IMP and compare this to the results of a second group known as a control group. An example of this is the double-blind randomized controlled trial in which the participants of the control group and the group that receives the IMP are randomly chosen. It is double-blind as neither the participants nor the administrators of the IMP are aware which group has received the IMP and which is the control.
The control group is sometimes given a placebo or they are given the best treatment option that is available and is the market leader for the drug that is being tested. This is known as the standard of care; the treatment of the disease that most physicians agree is the best.
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Why is the Standard of Care controversial?
The standard of care used in clinical trials has been subject to different interpretations and whether it refers to the best treatment that is available locally or worldwide. In many developing countries, the local standard of care is very limited or there is no care meaning that the clinical trials often use placebos on the control group and this creates a divide in the research and clinical trials.
Providing the best worldwide standard of care in all clinical trials may not be feasible and it can unintentionally obstruct significant research from these developing countries. This can lead to a bias and unbalance in the type of research conducted and what is considered significant in different parts of the world, making the scientific community skewed to the developed world. It can also be stated that control groups that use the local standard of care don’t cause harm as the participants would’ve reached the same outcome and level of treatment regardless of the clinical trial. Additionally, locally relevant research can incrementally improve the standard of care in that context, and depriving those populations would be unethical. A rigid yardstick has been researched for rehydration therapy when intravenous rehydration was the global standard of care and it has been a great advance in medical care.
However, the disparity in the standard of care around the globe is considered to be one that’s determined by the prices set by pharmaceutical companies, and therefore denying people the best treatment is unethical. A minimum standard of care has also been reviewed and considered to prevent harm and ethical violations. Additionally, research that is not challenging the world's best treatment methods can largely be scientifically irrelevant and meaningless.
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Developments in Standard of Care
There is no clear solution or answer to this dilemma. The Helsinki declaration which was developed by the World Medical Association in 1964 as a statement that outlines the ethical principles and guidance for physicians and researchers has similarly divided opinions and is also subject to various interpretations in regards to providing the best treatment available locally or worldwide.
The standard of care came under greater scrutiny after the clinical trials of zidovudine that were conducted in the 1990s. Zidovudine was an investigational treatment to prevent perinatal transmission of HIV and trials were conducted in many developing treatments. It came under fire and criticism when it was revealed that the control group was given placebos when there were alternative treatments available in developed countries. This led to initiatives to provide HIV treatment in developing countries and also the re-consideration of many guidelines involving international research.
The Helsinki declaration was modified to state the IMPs should be “tested against those of the best current” methods. Although it specifies the requirement to compare to the best medicinal product it still doesn’t clarify if this is a global or local context. With the lack of global guidance, some developing countries have set boundaries and ethical codes to prevent unnecessary deaths such as India and in response, clinical trials have been reduced by 93%. Without a global initiative to prevent this, people in developing countries will be exploited in the name of science.
The standard of care used in a clinical trial is vital as it forms the basis of comparison for the IMP in question. The lack of guidance and clarification of what is considered an appropriate standard of care can lead to research that is irrelevant when there are superior treatments available. In a small number of cases, it can provide suitable alternatives but this is usually at the expense of participants from developing countries where there are no laws in place to protect them from being exploited. There have been efforts by international bodies to regulate and enforce a minimum standard of care for clinical trials but with limited success.
References:
- Wendler, D., Emanuel, E. J., & Lie, R. K. (2004). The standard of care debate: can research in developing countries be both ethical and responsive to those countries' health needs?. American journal of public health, 94(6), 923–928. https://doi.org/10.2105/ajph.94.6.923
- Bhutta Z. (2004). Standards of care in research. BMJ (Clinical research ed.), 329(7475), 1114–1115. https://doi.org/10.1136/bmj.329.7475.1114
- Setting a Minimum Standard of Care in Clinical Trials: Human Rights and Bioethics as Complementary Frameworks. (2015, June 4). Health and Human Rights Journal. https://www.hhrjournal.org/2015/06/setting-a-minimum-standard-of-care-in-clinical-trials-human-rights-and-bioethics-as-complementary-frameworks/
Further Reading
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