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Framework to help design and review research involving children
  1. Bob Phillips1,2,
  2. Hugh T Davies3,
  3. Jennifer Preston4,
  4. Simon R Stones5
  1. 1 Centre for Reviews and Dissemination, University of York, York, UK
  2. 2 Health Research Authority, London, UK
  3. 3 Department of Paediatric Oncology, Leeds Children’s Hospital, Leeds, UK
  4. 4 NIHR Alder Hey Clinical Research Facility, Alder Hey Children’s NHS Foundation Trust, Liverpool, UK
  5. 5 School of Healthcare, University of Leeds, Leeds, UK
  1. Correspondence to Dr Bob Phillips, Centre for Reviews and Dissemination, University of York, York YO10 5DD, UK; bob.phillips{at}


This is the third of a series of four articles addressing ethical approaches and issues in undertaking clinical research with children and young people (CYP). This paper addresses the major ethical aspects of studies with CYP, where they vary from studies in adults.

  • ethics
  • health services research

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This article describes two sets of ‘Questions and Considerations’, one of a general nature and the second particular to this area that we believe can help both design and review research involving children and young people (CYP). We have deliberately avoided putting the word ‘ethics’ into our title as we believe what we are really striving for is no more than ‘good’ research!

General questions

Unsurprisingly there are huge similarities between research involving adults and CYP. Both require satisfactory answers to these questions:

  1. What is the research question, is it of relevance?

  2. Is the project building on what is known already?

  3. Can the method provide meaningful and valid answers to the research question?

  4. Are personal data handled appropriately (confidentiality)?

  5. When appropriate, is there satisfactory compensation for any injury caused by participation?

  6. Once the study is finished will participants receive appropriate care?

  7. Will the project be registered and results available in the public domain?

More details can be found on the following webpage: But there are also particular issues to research involving CYP or which give rise to different considerations.

Particular questions and considerations

  1. Is recruitment of CYP justified?

  2. Are CYP and their families involved in research design and its conduct?

  3. Are arrangements for consent, assent and dissent adequate?

  4. Has there been an assessment of possible consequences (benefits, harms and burden) and their management?

  5. Are any payments reasonable and not ‘undue’ influence?

  6. Do those conducting this research have appropriate expertise?

Is recruitment of children justified?

The researcher should be able to demonstrate the study will address a question which is relevant to CYP, families and professionals, a disease or condition unique to CYP, or one with particular issues in childhood.1 The James Lind Priority Setting Partnerships set a model as to how this might be done, involving all with legitimate interest.2

Past arguments have posited a further condition before research is undertaken, that research involving adults cannot answer the question. This comes from an past concept we should not expose CYP to any research risk. We feel this argument is excessively cautious as most research is of minimal risk, and there is even evidence of a research inclusion benefit.3 This is obviously tentative, but more research is clearly needed to establish or refute this important consideration.

Are children and their families involved in research design and its conduct?

This is explored in another article in our series.4

Are arrangements for consent, assent and dissent adequate?

Consent is agreement to a choice that meets the standards to make it legally and ethically valid.

While there are many similarities in ensuring freely given, informed consent is present in research involving adults, it is here that we find some key differences in research involving CYP. Young people may not be able to provide what would be deemed valid consent. In these cases we turn to a parent or adult with parental authority.

Fair (or ethical) consent needs the following:

  • A fair question: there should not be obvious, excessive or hidden disadvantage in any of the options offered (Hobson’s choice).

  • Information: this must describe the alternatives (all the choices available). The exact amount needed is a matter of judgement (and the subject of continuing debate), but broadly it should match the burden of the study (simply sending a questionnaire with an introduction and asking whether the recipient would complete and return it might be regarded as fair consent). More complex or demanding studies would need more.

  • Time: there is no mandated minimum or maximum. It should match the study burden.

  • Voluntariness: the process must be free of undue influence—helping people making decisions is fine, dictating to them is not!

  • Discussion and the opportunity to ask questions: evidence indicates this is the most important part of consent (but difficult to evaluate).

  • Ongoing opportunity to reconsider: in long-term studies, ensuring participants are happy to continue is good practice.

It also requires that those being asked are able to (have the capacity to):

  • Understand what the research involves.

  • Understand the alternatives to taking part.

  • Can retain the information long enough to make an effective decision.

  • Make a free choice, at the time it needs to be made.

And that those seeking consent:

  • Ensure the participant is able to decide for themselves (has capacity): those seeking consent need expertise and experience in this area. The competence and training of those seeking consent are central to fair consent.

  • Provide adequate information and time: this is a matter of judgement (and dispute!) but should be proportionate to the study. When uncertain, researchers should consult potential participants.

  • Check understanding: this is not often undertaken but is important if the research is more than minimal risk or there are ‘key issues’.

  • Ensure they do not exert undue influence: helping people make decisions is fine, dictating to them is not.

As many CYP will not be able to provide consent, two approaches have been developed for research.

The first is to define an age below which consent must be provided by the adult with parental responsibility. As an example, this is required in the Clinical Trials of Investigational Medicinal Products (CTIMP) conducted in the European Union (EU). Here, consent must be obtained from parents if the CYP is less than 16 years old, regardless of their established capacity.

The second is to rely on assessment of capacity at the time, and if the CYP can meet the criteria above they themselves can provide consent. For this, the researchers must show they will determine whether the child wishes to be involved, be able to demonstrate they have the skills to assess capacity and then seek consent.5 Those assessing capacity should demonstrate they are aware of the following:

  • The relationship between age and different aspects of competence.

  • That the child’s experience of illness will alter this.

  • That they must provide information in a format the child is best able to understand.

  • The need to ensure the child can make the decision free of ‘undue’ influence, accommodating the usual freedom to decide the child has.

Assent is agreement made with time, methods and information that are appropriate for the person’s capacity but not to the criteria that would make it legally valid (‘consent’).

Regardless of which of these two is used, the CYP must have the opportunity to contribute to any decision (assent), depending on their maturity, capacity and the nature of the decision. It is axiomatic that we should always tell CYP what we propose to do, according to their understanding. In doing this we can also seek their agreement, even when we seek consent as authorisation elsewhere. As an example the EU Clinical Trial Regulation 20146 requires:

the minors have received the information referred to in Article 29(2) in a way adapted to their age and mental maturity.

Assent is thankfully poorly defined in law, freeing researchers and reviewers from the requirement to provide ‘complete’ or ‘comprehensive’ information. Rather it must be relevant and understandable (‘comprehensible’) to the CYP and match their capabilities. Researchers should:

  • Think of how and when to talk to the family and CYP and how any material will fit into this.

  • Judge what would fairly represent what would be ‘in a way adapted to their age and mental maturity’ and what the CYP need to know using appropriate media.

  • Test materials with CYP.4

  • Accommodate opinion from all—CYP, parents and professionals.

  • It is crucial to recognise this should not be an approach which just ‘distils’ the ‘adult/parent’ process and patient information summary, rather it must be properly adapted to consider the CYP angle.

Dissent is a refusal to cooperate or do something.

At the outset, if there are disagreements within a family, be those between parents or parents and the CYP, over enrolling in research, the CYP usually is not recruited. There would need to be very clear reasons to over-ride objections. While this issue is often discussed in ethical committees, in reality it is much more usually a shared decision and rarely a problem in practice.

As research progressed, handling a lack of agreement (dissent) can sometimes be difficult. At what stage do we believe we should stop? It could vary from flinching during an uncomfortable or painful research procedure to diving behind the sofa or even refusing to attend the next research visit. Guidance leaves this decision to the researcher and the family. At a minimum a trial procedure should be stopped if the CYP dissents. There should be a short pause to allow the child to settle, involvement of parents and then further explanation. An assessment of the situation may be needed to reassure the child, or to decide to definitely abandon the procedure and perhaps even withdraw from the study.7

Has there been an adequate assessment of consequences (benefits, harms and burden) of the choices before the CYP and family and management of possible research harms and burden?

This is central to the design and review of all research, but there are particular issues in research involving CYP as consent may come from a parent and not the child. There is also public sensitivity about enrolling children into research (however mistaken this may be), hence the importance of seeking CYP’s and families’ views on the acceptability of the consequences of any study.

The benefits, harms and burden of alternatives to joining the research (the choices before the CYP and family)

These are germane to any decision (consent) and should be outlined to inform the choice.

Benefits of the research

The benefit of research is answering a research question to improve care or develop understanding. To meet this researchers must be able to demonstrate relevance of the research question and that answers will be meaningful (providing evidence to found care and broaden knowledge) and valid (we can have a degree of confidence in the results). If required this should be confirmed by (1) independent peer review along with methodical review of prior work, (2) a proportionate review of current evidence, and (3) CYP and family consultation. For some projects the purpose is to provide training in research method, but this still requires a demonstration that the project meets the standards of good research practice.

If there is little or no clear purpose (no external consequence and benefit), any possible risk will be more difficult to justify and it is likely that reviewers will take a much more cautious position. Harms will need to be minimal.


Review will concern itself with the possible harms of the research itself, so in any therapeutic or clinical research it is important to define the harms from taking part in the research itself. In much research the consequences are immediately evident, but in clinical research it is important to separate the risks and burden of the disease, and its usual treatment, and from those created by the proposed research. Patients will carry the risk of their condition whether or not they are in a research study, and the treatment undertaken may or may not be a risk of the study.

As a principle, the risk of harm from any research intervention or extra procedures should be minimal or less. The following are two commonly used definitions:

The research bears minimal risk if it is to be expected that it would result at most, in a very temporary negative impact on the health of the person concerned. We believe this is the most acceptable definition in practice. 8

Or everyday comparison:

The probability and magnitude of harm or discomfort not greater in and of themselves than those ordinarily encountered in daily life or during the performance of routine physical or psychological examinations or tests. 9

In research comparing treatments, it is argued that there is no putative risk (at least less than minimal risk) if there is ‘equipoise’ or ‘uncertainty’ as to which treatment is better.

Most research meets these criteria, and certainly any project carrying greater than minimal risk requires careful consideration. It will not, de facto, be unethical in CYP practice; this will depend on the balance between this risk and the benefits. The ad hoc EU committee on implementing the clinical trial directive produced a useful table suggesting a categorisation of risk.10


The burden of the research, the extra appointments and tests and questionnaires, should be reasonable in respect of the intent of the study.

The research team needs to show how all risks of harm and burden have been minimised and commensurate care for such eventuality is in place. Examples would be the following:

  • Combining research and clinical procedures whenever possible.

  • Indwelling catheters used when possible.

  • Microassays should be used with small volumes required.

  • Use of scavenged blood remnants.

  • Monitoring of actual blood loss.

  • Age-appropriate explanations to reduce fear.

  • Facilities appropriate to children with trained personnel.

  • Timing of sampling coordinated with daily activities.

  • Sampling performed by trained staff, with a limited number of attempts for sampling.

Are any payments reasonable and not ‘undue’ influence?

Families should not be out of pocket if they take part in research, so any expenses (if any) for the CYP and those for the parents should be met. Other payments for CYP are contented.

It would seem only fair that CYPs are paid if adults are yet in a CTIMP this is seemingly illegal; the Medicines for Human Use (Clinical Trials) Regulations (2004) explicitly prohibit the giving of incentives or financial inducements (except provision for compensation in the event of injury or loss) to children (under 16 years of age), and in the UK the Royal College of Paediatrics and Child Health’s ‘Guidelines for the ethical conduct of medical research involving children’11 similarly state that researchers must ‘offer families no financial inducement, although expenses should be paid’. Broader principles and models on payments to research participants can be found in ref 12.

Do those conducting this research have appropriate expertise?

These are difficult issues on which to make reliable judgements, yet are central to ‘fair research’.13

There is the more reliable safeguard provided by the presence of an intelligent, informed, conscientious, compassionate and responsible investigator.

Researchers should have and be able to demonstrate the necessary skills for their roles, such as the following:

  • Documented experience and training in childcare, paediatrics and relevant subspecialties.

  • Expertise in appropriate, similar clinical trials with neonates, children or adolescents.

  • Relevant experience in sample collections/tests/X-ray/measurements in neonates, children or adolescents.

  • Specific expertise for explaining studies, seeking consent and the preparation of information material for informed consent/assent to children and family members.

  • Additional training for clinical trials (good clinical practice certification or equivalent) and including data protection, safety reporting and ethics guidelines.

  • Competence and training in procedures, policy, national laws and regulations, and requirements for trial-related issues.

  • Safeguarding and child protection training as appropriate to the risk of the study.

In addition there needs to be appropriate legal, institutional and professional accountability, and researchers also need to understand their duties as a healthcare professional, separate from the research, to identify and resolve potential conflict between interests of a healthcare professional and a researcher.

Students should have appropriate supervision; just as trainee doctors undertake the care of patients with supervision and support, trainee researchers undertake studies in the same way.


We have truthfully hesitated before adding further ‘guidance’. Library shelves groan at breaking point, and the data clouds above get darker and darker. Torrential floods of guidance might be imminent.

No guidance or framework will give us the answers (what is right or wrong, good or bad, ethical or unethical), and we are still left to make the balancing judgements. We also acknowledge that while the questions may be simple, the answers may not be (although as guidance to applicants we would urge that simple questions are best simply answered), and expertise may then be needed. The model also will take us some but not all of the way towards consistency of judgements and decisions. Attempts to do this currently would drive wedges between the groups involved in research rather than bring them together.14 This framework would be a foundation to take this further.

So we justify this paper as a shape to review rather than generation of new guidance, and as a ‘framework for thinking’ rather than ‘rules to be followed’. It encourages us to be explicit about the reasons underpinning our positions, judgements and decisions. We believe this can help both researchers when they design their project and reviewers when they undertake their review, and (as a final impoverished defence) it can be found in other areas.15–19




  • Contributors HTD, BP, JP and SRS all designed and debated on the series of articles, made editorial comments, and assure the validity of the content. BP drafted this article initially, with comments and involvement from all authors.

  • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors. RSP is funded with an NIHR Post-doctoral Fellowship (10872)

  • Competing interests None declared.

  • Patient consent Not required.

  • Provenance and peer review Commissioned; internally peer reviewed.