69
Research and consent

Research

Health professionals wish to provide the best possible care for newborn infants. This should be evidenced-based, but this is only possible when evidence is available from properly conducted research. It is therefore unethical for properly conducted research on newborn infants not to be performed. Failure to do research leads to stagnant and second-rate medical care.

Research may be interventional, e.g. evaluation of a new therapy, or non-interventional, e.g. descriptive or observational (Table 69.1).

Table 69.1 Differences between interventional and non-interventional research.

Interventional (therapeutic) research
Research which directly affects the treatment an individual receives. They may receive a new treatment or, in a randomized trial, a new or conventional treatment or placebo. At the start of the project the answer to the question about which treatment is better will not be known (equipoise). Use of a placebo instead of treatment is unethical if there is an accepted treatment. The new and potentially better therapy should be compared with accepted treatment.
Non-interventional (non-therapeutic) research
Research that will not benefit directly the person involved. This is observational research – e.g. the normal levels of vitamin A in a particular group of infants. The infants themselves will in no way benefit – so the invasiveness of obtaining the information must be minimal (a small extra volume of blood when venepuncture is required for other reasons, or a single venepuncture, well performed with analgesia).

There are a number of obstacles to overcome in order to perform research in newborn infants. These are practical and ethical.

Practical difficulties in conducting research in infants

These include:

  • The number of newborn infants who are preterm or have a specific problem or condition is small and usually requires trials to be multicentered, which adds enormously to the complexity and cost of each study. However, a number of networks have been established to facilitate this, such as the Vermont–Oxford and NICHD (National Institute of Child Health and Human Development) Neonatal Research Network and the Canadian, Australian and New Zealand, Italian and other national neonatal networks and many multicentered trials have been performed throughout the world (see Cochrane neonatal reviews).
  • Funding is difficult to obtain as the number of newborn infants with a specific problem is small, making pharmaceutical companies less likely to develop new products or conduct trials.
  • In order to proceed with a trial, the information required about a potential new drug or therapy is becoming ever more stringent.

This also applies to pilot studies, making it increasingly difficult to obtain the data required to conduct a larger study.

Ethical difficulties in conducting research in infants

All research must be peer-reviewed and sanctioned by an independent ethics advisory committee – Institutional Review Board in North America, appropriate research ethics committee (REC) in the UK.

Parents must be able to make informed choices when asked to give consent for their infant to take part in research. This can be problematic when decisions need to made rapidly, e.g. when a baby suddenly becomes ill, especially immediately after delivery, when parents are emotionally stressed. Key factors of informed consent are outlined in Table 69.2.

Table 69.2 Key factors in informed consent for research.

Diagnosis – include description of medical steps leading to the diagnosis
Research – nature and purpose of proposed research
Risks – common risks, less common but severe risks (such as death, brain damage, loss of organ function)
Alternatives – other options, including their risks and benefits. It is always an option not to participate in a study and to receive standard therapy

Criteria for informed consent for research include:

  • Competence of the person giving consent.
  • Information – sufficient for informed choice, including a written information sheet for parents and the use of an interpreter if there are concerns about the parents’ understanding of English.
  • Understanding – parents must have understood the research sufficiently to be able to evaluate choices. In the US and UK, consent can be provided by one parent with parental responsibility; in some countries in Europe both parents must agree.
  • Written consent should be obtained, with one copy for the parents and another filed in the case record.
  • Voluntary – parents must be aware that they can decline or withdraw from the research without jeopardizing their baby’s care.

All large multicenter trials have a Data Safety and Monitoring Committee which ensures the safety and well-being of the participating subjects. They have the power to terminate enrollment if they have the evidence that the intervention is harmful or if continuing the study cannot demonstrate benefit.

Consent in clinical practice

Health professionals are under pressure to allow parents greater involvement in decision-making and enable them to give consent to treatment.

Parental consent should be obtained for complex procedures or treatment and for all surgical procedures. Documentation about the communication with the parents explaining the basis, benefits and risks of the procedure or treatment is more important than obtaining a signature on a consent form. Consent for a surgical procedure must be obtained by someone familiar with and capable of performing the procedure. For infants receiving intensive or special care in a neonatal unit, it would be impractical to obtain detailed consent from parents for the multitude of low-risk procedures performed on their baby. However, parents should be given an overview about what the care of their infant involves and what range of procedures will be performed, both verbally and in an information booklet.

In clinical practice, consent is most problematic about the initial resuscitation and immediate management of extremely premature infants at the limit of viability and when withdrawal of treatment is being considered. The former is considered in Chapter 13 on neonatal resuscitation, the latter in Chapter 68 on ethics.