Many students of medicine will possess a natural curiosity about the underlying processes of disease and how the body works. In the UK, the sciences are a requirement at A-level for applying to medical school and the scientific method of acquiring new knowledge via the process of hypothesis, test and repetition is likely to have formed a key part of the curriculum.
Medical research often follows a similar scientific method, where hypotheses relating to new pharmaceuticals and disease processes undergo rigorous testing. However, medical research is surprisingly not a simple binary field of success and failure, every patient has a subtly different physiology and while some drugs may be effective for the majority, it may not be for some. This leads to medical research and practice taking on an experimental nature, working to find the best solution for the greatest number of people. This means that a careful and considered approach to medical research must always be taken, owing to this uncertainty as well as the potential for harm to the patient.
The fields of research within medicine are vast and while the best known might be the development of new treatments or pharmaceutical agents but this only scratches the surface of what research goes on within the medical field. Several broad fields exist looking at patterns and incidence of disease, management of healthcare systems, legal issues and areas where medicine and sociology intersect.
This wide purview means that it is hard to find a set of governing principles that cover all these fields, but some do exist and in this section, we will discuss some of the ethical issues that these principles apply to as well as unresolved issues and tensions that continue to underlie medical research today.
Research in Medical Practice
As a medical professional, you will be exposed to huge amounts of medical research as you progress through your studies, developing skills on how to interpret and parse the data in an efficient manner. This will serve you well as you begin to practice medicine as all doctors must stay up to date with research in order to keep their skills in line with the most current recommended practice, even if you do not participate in research yourself.
Furthermore throughout your time in medical school, there will be multiple chances to get involved in medical research and exposure to academics working at the top levels of their field. Therefore it’ll be useful to briefly cover the structure of research in medicine. The most common method of conducting research is the clinical trial – testing new therapeutic agents for both how effective they are in treating and to ensure they are safe to use. Most research into pharmaceuticals starts out in lab based studies, often investigating the effect of therapeutic agents on cells under a microscope. This is then followed by animal testing to attempt to predict the effects of the agent before finally progressing to clinical trials. These clinical trials will go through 4 stages or phases 1:
- Phase 1 – A trial is carried out on a small number of healthy volunteers. The purpose here is to ascertain the appropriate dosages to produce the desired effect as well as seeing if there are any dangerous side effects
- Phase 2 – The trial is then carried out on patients who have the condition for which the agent is targeted. This will help determine what the impact of the drug is and what side effects, if any, are produced
- Phase 3 – A large scale clinical trial, often involving many doctors working across several countries, comparing the agent to another drug or a placebo (a pill that has no effect). The most statistically robust form of these trials are “double blinded” – meaning that both the patient and the doctor giving the drug know whether the patient is receiving the agent under investigation or the placebo
- Phase 4 – This stage occurs after the drug has been licensed for usage and is essentially a follow up of the drugs administration for a few years, to check there are no unexpected side effects that may be delayed in their presentation
This perhaps illustrates the long and complex process that any new drug must undergo in order to be approved for use. While thorough testing is of course necessary to ensure safety and definitive results, the amount of time and money that is necessary for product development and approval can be vast, stretching into the billions of dollars (a recent report found it to be on average around 2.6 billion US dollars 2) and 20-30 years for a new pharmaceutical agent to go from the drawing board to the pharmacy.
Given how much is at stake, it is easy to see how the role of the doctor as a carer and the doctor as a researcher may start to conflict. While of course the patients’ health must be the first priority, the huge investments necessary to bring a product to market will exert a pressure for results and strong principles are required to resist these external pressures.
Ethical Principles in Research
Many of these principles arose in the 1940’s and 50’s following World War 2 and the terrible crimes committed by doctors under the Nazi regime. Following the Nuremberg trials investigating war crimes carried out during WW2, the Nuremberg code was established. These principles were developed over the years to cover all the broad areas mentioned previously and were eventually codified into a summarised form in 1964 – the Declaration of Helsinki (DoH) 3. Since then, it has undergone several updates and is generally recognised as the guiding set of ethical principles that must be applied to all medical research going forward.
There are also several other bodies that have produced more specific guidance, both internationally and within the UK, but the principles outlined by the DoH are broadly similar and many of those outlines have since been made part of national laws around the world. These principles include:
Ensuring Informed Consent
This is the very first principle set out by the Nuremberg Code, establishing that “the voluntary consent of the human subject is absolutely essential” and that the participant “should have sufficient knowledge and comprehension of the elements of the subject matter involved as to enable him to make an understanding and enlightened decision.” This will involve clarifying any risks that the trial may entail as well as the potential benefits
The declaration elaborates on this principle by specifying the details about the project that the potential participant would need to know in order to make an informed decision about consent. It also recommends that informed consent can be established by the signing of a consent form (which normally has been evaluated by an ethics review committee prior to starting). However, the process of consent is not just limited to signing the form, but must also involve a clear explanation of the project of what participation in the study will entail. It must also be clearly stated that the participant is free to withdraw from the project at any time, even if the study is already underway.
The DoH also contains guidelines to deal with conducting research with those who cannot consent, whether due to young age or disability. These conditions do not preclude research from being carried out on these patient groups but there are much more stringent rules that must be followed.
The inevitable result of research will be the publication of data to the wider scientific community all of which will be publicly available. This means that researchers have a responsibility to ensure patients are aware and informed of this, even if their identifying information will be removed and all personal data will be held securely.
The research project must be scientifically worthwhile and of value socially
The declaration makes clear that any research on humans must be justifiable on a scientific basis and is not going to produce results of an unimportant nature. This results in projects establishing a solid knowledge base before application, whether through a prior literature search of existing research or animal and lab studies.
The research must also be of sufficient social impact or use as to justify the expense of funding. As mentioned before, medical research can be a hugely costly process and given a limited pool of funding, any studies supported must be demonstrated to have a positive impact. Any research should also be of benefit to the populace from which participants are recruited from, so that one group of people does not benefit from research where another group has shouldered the risk.
Honest Reporting of Results
There have been several widely publicised stories surrounding fabrication of results, reaching to the very highest and most respected academics. While, this may be an obvious point, perhaps what is less recognised is the knock on impact of dishonest reporting of results – not only in impacting patients with clinical practice being influenced by false assumptions, but also on the rest of the research community. Trust is eroded in the nature of these clinical trials and time and energy is expended on confirming these results or conducting follow on studies based on the erroneous data
The declaration makes clear that before research is carried out, it must now be subjected to ethical approval in order to demonstrate that a project is worthy, that participants are informed and aware of any potential risks and benefits and that any potential harm will be minimised as much as possible
Every proposal for medical research on human subjects must undergo approval by an independent committee before being given assent to continue. The methods and purpose of project must be explained, as well as the recruitment and consenting process. Any funding sources or conflicts of interest must be declared from the outset. These committees may also monitor projects underway to ensure that the project is adhering to the outline that received approval.
Despite these principles and what may seem like a rather convoluted process to be able to conduct medical research, several issues in research still remain
There are currently several hot button issues in medical research such as stem cell research which has been the topic of much debate over whether it is morally acceptable. As science advances, the question is no longer solely “can we do it?” but also “should we do it?”
Other concerns include the issue of whether a placebo should be used and in what conditions would it be fair to those not receiving an intervention. Sometimes if an intervention is clearly advantageous compared to placebo, trials may be halted early as it would be unethical to continue using a placebo, but the point at which this should occur is not entirely clear.
- Medical research is not an exact process and can be extremely time and resource consuming
- The good medical professional will stay up to date with modern guidance on research in order to keep their practice at the forefront of medicine
- The Declaration of Helsinki provides a useful broad set of principles for dictating an ethical approach to medical research, with an emphasis on consent, confidentiality, assessment of risk and benefit and ensuring ethical review of all research
- Tensions still remain, over the influence of large well-funded interests, when to use placebos, moral questions over research and the focus of research. There is a “10/90” gap whereby 10% of medical research resources are focussed on health problems that affect 90% of the world’s population
1 DeMets, D., Friedman, L., and Furberg, C., (2010). Fundamentals of Clinical Trials. Springer 4th Edition
2 DiMasi, J., Grabowski H., and Hansen R., (2014). Innovation in the Pharmaceutical Industry: New Estimates of R&D Costs. Tufts Center for the Study of Drug Development (slides accessed online 29/08/2015 at http://csdd.tufts.edu/files/uploads/Tufts_CSDD_briefing_on_RD_cost_study_-Nov_18,2014..pdf)
3 World Medical Association (2013). “Declaration of Helsinki: Ethical Principles for Medical Research Involving Human Subjects”. JAMA 310 (20): 2191–2194.