Clinical research is a crucial partner to best clinical practice. It can include the study of disease prevention and causation, diagnostic tests, new or different treatments, and the prognosis and outcomes of different conditions.1 Clinical trials are a specific form of research designed to find out the effects of an intervention, where the intervention may be a drug, a surgical or diagnostic procedure or a device.2 When deciding if a treatment or intervention is beneficial or otherwise (whether it improves outcomes), appropriate testing of the intervention will often involve a clinical trial, in a randomised or cohort type of methodology.
Research methods have been developed to minimise bias in clinical trials; these include randomisation and ‘blinding’ or ‘masking’ of participants and researchers to the identity of agents or procedures being compared. The very use of such methods implies ethical issues that must be addressed with participants. Human research is unique in that human beings have the capacity and right to make decisions for themselves. In clinical research, this brings about the requirement for informed consent. This requirement has the following conditions: consent should be a voluntary choice, and should be based on sufficient information and adequate understanding of both the proposed research and the implications of participation.
All principles that guide our conduct when undertaking clinical trials have their origin in the World Medical Association’s Declaration of Helsinki.3 In the Australian research environment, the National Health and Medical Research Council plays a role in providing guidance and advice to researchers as well as those that are involved in their approval and conduct, such as ethics committees.4
From the perspective of the team
From the perspective of the research team, clinical research of any type is time consuming, resource intensive and expensive. Many processes need to occur before a researcher even has an opportunity to discuss their study with a potential participant. All clinical research trials involving an intervention ideally commence with a clinical situation in which, after a thorough search of the literature, there remains insufficient evidence to inform the best course of treatment. By the time a clinical research trial is recruiting participants, the trial protocol has been reviewed by a human research ethics committee that will include a scientific review, if this has not already been done. If the particular trial has funding, it will also have been peer reviewed for scientific merit and methodological rigour by the funding body. Clinical trials running within publicly funded institutions also undergo a governance review, which ensures that the institution can support the research trial and that all costs, including monetary and time, have been accounted for and will not burden the institution.
In our experience, we have found that it is essential to engage with clinical staff working in the setting in which recruitment will occur. It is important that a research culture exists and that clinical staff have been presented the trial protocol, including the rationale and procedures. Research is core business within public teaching hospitals and for this culture to exist, clinical staff should be aware of the process that has happened before recruitment commences. That is, research gap demonstrated, lack of evidence for the clinical situation, scientific and ethical approval – and importantly, the rights of potential participants to have access to a treatment that may be beneficial and would otherwise be unavailable.
Research staff should work within all clinical settings with great sensitivity to priority of clinical care of potential participants. Clinical staff within public hospitals are working in stressed environments that are often under-resourced. Clinical care is always a priority and research should fit in around the clinical priorities. Ideally, participation in a trial should be presented as part of clinical care, with the clinician discussing the management plan and the study with the patient. If relevant, the clinician should explain that best treatment for the condition is currently uncertain, and a trial is available that may or may not benefit the participant, but will assist clinicians to gather high-quality evidence that will benefit other patients in the future.
Any processes that are put in place to assist recruitment to clinical trials should consider the clinical scenario (that is, the busy outpatient department, antenatal clinic, elective theatre or delivery suite) and aim to enhance the experience of the woman as the potential participant. Despite researchers considering different tools to increase the understanding of participants, it is apparent that a study team member taking time to talk individually to potential participants is the best approach.5
Barriers to obtaining consent
For a clinical trial to be considered by a woman/participant, it should ideally be introduced by a clinician, either a midwife or obstetrician who is supportive of the research, who is able to answer any initial questions the woman may have. As researchers, we often find that participants have been actively discouraged to be involved with research, as a direct or indirect result of negative views expressed by the clinicians providing their clinical care. Another significant barrier for gaining consent and participation in trials occurs when clinicians offer the experimental treatment outside of the trial. This hinders both opportunity to accrue participants and evidence for best clinical care.
Practical aspects of consent
There are many ethical guidelines to obtaining consent.6 For a detailed assessment and explanation of risks and benefits as they pertain to consent, we refer the reader to the NHMRC National Statement on Ethical Conduct in Human Research.7 Here we provide what we deem, in our experience of working in perinatal clinical trials, to be some of the important points to consider. Trial information should be provided in verbal and written forms, and written informed consent is then obtained from the participant. When counselling, it is important to consider the points listed in Box 1.
It is always important to allow sufficient time (when possible) for the woman to: consider participation in the study; ask questions; discuss with partner, family, other support person or healthcare provider; and then be able to answer questions. Documentation in medical records should indicate that trial information has been provided and whether the woman consented or declined.
There are several unique aspects and ethical considerations when obtaining informed consent for perinatal trials, our area of interest and experience. Situations such as when women are in labour, expected to deliver preterm, or their baby is expected to require intensive care or be otherwise unwell at birth, can prove difficult for obtaining consent. At these times, women and their families are often anxious and overwhelmed and there will be varied essential clinical care to be given. The wellbeing of the woman and baby should always take precedence, but it is possible to provide information about clinical trials in a sensitive and appropriate way. There may be limited time to obtain consent if birth is imminent and, if consent is obtained in this type of situation, it is worthwhile seeing the woman a day or two after the birth to discuss the trial in more detail.
Antenatal interventions, especially drug trials, bring another aspect of complexity to consent. Women are often hesitant to expose the fetus to drugs unless absolutely necessary and don’t want their baby to be a ‘guinea pig’. The issue of drug trials in pregnancy is a complex one, highlighted by a recent article by Scaffidi and colleagues,8 which was the subject of an interesting Twitter-based discussion on the same subject. The authors report that 0.32 per cent of all active registered studies on clinical trials registers were perinatal drug trials.9 It is likely that this is multifactorial in cause, but in our experience, the degree of administration and frustration associated with approving perinatal drug trials, even to the point of being able to approach a participant for consent, is inversely proportional to the aforementioned percentage.
Box 1. Points to consider when obtaining consent for clinical trials
- The aims of the study
- What we know and don’t know about the clinical condition
- Who is eligible for the study
- Whether the study is comparing a new treatment with control or new treatment with current standard care
- How and why random allocation to one of the two groups will occur
- Why there is blinding to treatment group and reasons/advantages of this
- Comparison of outcomes, what outcomes we are interested in and why
- What participation involves for the participant
- What is additional to standard care
- Participant may or may not benefit
- Potential risks and benefits
- Participation is voluntary, able to withdraw at any time without effect on care received
- Privacy and confidentiality
- Research team to have access to medical records for relevant data collection
- Collection of contact details for participant and other supports
- Respect for culture
- Consider those with low literacy/educational background – use appropriate language
- Is an interpreter required? Can partner/other family assist?
- Are you comfortable the patient understands what is involved to participate; is it ‘informed’ consent?
The establishment and coordination of a clinical trial is an expensive, resource-intensive undertaking. The need to address a clinically important research question must be demonstrated, funding obtained, the necessary approvals sought and study materials and procedures developed. A research culture and a keen local investigator with the support of clinical staff are vital to the successful running of a trial. Whenever the clinical situation allows, potential participants deserve the opportunity to consider the study information and make the informed decision to take part in a trial that may benefit themselves or their baby. The importance of the support of clinicians who are willing and able to counsel potential participants and seek informed consent cannot be underestimated. The successful completion of a clinical trial within a reasonable timeframe can provide evidence that changes clinical practice, benefits patients and may save valuable health resources.