Clinical Research

Scenario 1: Who Decides?

Type 2 diabetes is becoming an issue of national importance for all Canadians. However, there are certain populations, such as Aboriginal peoples, who are at particularly high risk for this disease. Your research group is creating a new diagnostic test for patients with type 2 diabetes which identifies genes that may influence insulin function. Selecting and then carefully monitoring individuals who are at increased risk is an important method of achieving early diagnosis and improving the overall health of these patients.

You have been contacted by a local Aboriginal community who would like to develop a partnership with your research group in order to study and eventually improve the overall health of their community. You would like them to participate in your health research about type 2 diabetes, which significantly impacts their community. However, during an initial meeting with community elders, you discover that they are primarily interested in participating in research about a rare form of arthritis that has plagued their band for generations. What should you do? You want to treat the Aboriginal community members as partners in the research process and serve their stated needs as suggested in TCPS2. Yet, you are confident that conducting your health research about type 2 diabetes could lead to important discoveries that could benefit all Canadians in addition to this Aboriginal community.

Discussion questions:

  1. What are some of the key ethical issues involved in this case?
  2. Why should some communities be given special consideration in the design and conduct of health research?
  3. What would be some of the potential outcomes if you decided to go ahead with the arthritis research study? Or only agreed to conduct your research about type 2 diabetes? Or decided not to conduct research with this community at all?
  4. Would your decision change if this case involved a different community, such as a particular religious group? Or a different health topic, such as alcoholism?
  5. How would your viewpoint differ if funding was already in place with this community to conduct your research about type 2 diabetes?
  6. Would you feel differently if the community was primarily interested in looking at heart disease, as you could relate this to your diabetes research?

Scenario shift:

After discussing your concerns with the community elders, they inform you that they will agree to fund the arthritis research study. They suggest that you start with the arthritis research and then later, if funding levels permit and their community approves, you can move on to the type 2 diabetes research you originally wanted to conduct with the community. However, they are clear that they cannot guarantee any future funding for a variety of reasons.

Additional discussion questions:

  1. How does the availability of funding for the arthritis research from the community change the ethical dimensions of this case?
  2. What are some of the pros and cons of this funding arrangement? How does this arrangement differ from funding received from CIHR?
  3. As a researcher, do your responsibilities change in this case? Who would you be responsible to if you agreed to conduct research funded by this community?
  4. Who should set a research agenda? Who should pay for health research? Is it acceptable for a community to pay only for research that interests them?

Relevant ethics guidance document:

Links to the Ethics Cycle conceptual framework:

  • Through this scenario, participants can address issues under the following topics:
    • Forming research question (how research questions are formed impacts stakeholders of research outcomes) (KC).
    • Designing project (choice of collaborators can impact the design of a research project as well available resources and methodologies used) (KC).
    • Adapt knowledge to context (research should give voice, power, and agency to research participants) (KT).

Link to real life case study:

Discussion Guide:

  1. Key ethical issues to be considered include: conflicts of interest; resource allocation; utility and benefit; and responsibilities to funders, communities, research participants, and the Canadian public.
  2. Issues such as: respecting different value/governing systems, historical, and other contextual factors; collaboration and trust in research; differing health needs; success and translation of research; etc., should be discussed.
  3. There are many possible outcomes that can be discussed including: not fulfilling responsibilities to a funder; loss of trust; detrimental/beneficial implications for collaborative ongoing relationships; tradeoffs concerning meaningful research results that are beneficial to some versus meaningful research results which are beneficial to many; advocating the needs of an underserved community; etc.
  4. Issues of stigma and discrimination of certain groups, and overall benefit, utility, effectiveness of the research, etc., should be discussed. Promoting the interests of the underserved communities could also be considered.
  5. Responsibility and obligation to funders are important considerations here. Research integrity, resource allocation, and distribution of benefits are also relevant issues that should be discussed. What are some of the potential outcomes that stem from changing health topics when engaged in a funded research study?
  6. The scope of the originally approved research/ research funding plays a key role in choosing the appropriate course of action.
  7. The availability of funding may result in a conflict of interest as the researcher may allow the interests/expectations of the funders to inappropriately shape the design and conduct of the research, for example. It also raises issues of fairness and responsibility (to researchers, funders, the community, and the broader Canadian public).
  8. Issues to be considered include: fostering community consultation and collaboration in research; maintaining scientific rigor and appropriate use of methods; building and maintaining successful relationships. Research with an Aboriginal community (that is also funded by this community) will involve respecting the specific community values, desires, governance structure, and expectations, including adhering to the policy on research involving such groups (see TCPS2, Chapter 9).
  9. Responsibilities change both because the community is the research funder (and therefore you are responsible to them as both funders and participants) and because of the special considerations involving research with Aboriginal communities outlined in TCPS2, Chapter 9.
  10. Issues to be discussed include: the need for collaboration in establishing the goals, methods, etc., of the researcher; societal and community obligations to fund research; and wider social justice concerns.

Scenario 2: Research with Children and Young Adults

You are researching a new drug for the treatment of leukemia that avoids many of the common side effects of chemotherapy such as vomiting and nausea. It is just about ready for Phase III clinical trials. While the leukemia you are investigating primarily affects young children, you are considering doing the trial on young adults who usually experience a less severe form of the leukemia. Your decision is partly influenced by the fact that you have heard that to be considered ethical, research with young children involves many extra steps and delays. For example, your team would need to develop unique communication tools and recruitment strategies specifically designed for young children. Consequently, your team decides to test the drug in a young adult (mature minor) population to avoid these extra tasks.

Discussion questions:

  1. Is this research scientifically valid? And if not, what are the ethical implications?
  2. What are the costs of not doing research with younger children?
  3. What are the costs of delaying your research? Who may suffer?
  4. Would your opinion about this case change if the child subject group in question were healthy? What are some of the ethical issues associated with doing research with healthy children?

Scenario shift:

You commence your research with the young adult population. You are nearing the end of your recruitment period yet the preliminary results of the Phase III trial appear not to be statistically significant. You believe that this is because the inclusion population has a milder form of the leukemia and so the drug does not appear to be efficacious. You think that expanding the trial to include younger children with a more severe form of the leukemia may demonstrate a statistically significant benefit of the new drug.

Additional discussion questions:

  1. Is it problematic to change methodology during a project to achieve statistical significance? What are some of the pros and cons?
  2. When can an ‘adaptive design’ approach to research be justified, if ever?Footnote 1

Relevant ethics guidance documents:

Links to the Ethics Cycle conceptual framework:

  • Through this scenario, participants can address issues under the following topics:
    • Toward continued KT (how researchers allocate resources impacts future knowledge production and translation) (KT).
    • Review and select knowledge (how researchers select knowledge can lead to biases and blind spots when results are translated) (KT).
    • Analyze data, recruit participants (subject selection impacts the methodological choices available to researchers and how results can then be analyzed) (KC).

Link to real life case study:

  • Caldwell et al. (2004) discuss the ethics of conducting research with children and the benefits of having children participate in research. One area of research that has been particularly successful in addressing the issue of therapeutic orphans is pediatric oncology clinical trials. Caldwell, P., Murphy, S., Butow, P., & Craig, J. (2004). Clinical trials in children. Lancet, 364(9436), 803–811.

Discussion Guide:

  1. Topics such as scientific background and rationale, justification, equipoise, research objectives, methodology and ability to meet research objectives and adequate statistical power should be discussed. Appropriate peer review may examine and highlight these factors. If research is not scientifically valid it cannot be considered ethical. ‘Bad’ science creates unnecessary risk, undermines the research endeavor and public trust, wastes resources etc.
  2. The cost of not doing research with younger children leads to children being left as therapeutic orphans. In other words, although their exclusion protects them from the risks of medical research, they may also fail to benefit from this research.
  3. Delaying research may result in prolonged and unnecessary suffering of those treated using traditional chemotherapy treatments (including death). Also, additional research dollars may not be used effectively/could have been allocated elsewhere.
  4. Whether research is considered ethical or not relates to the balance of harms and potential benefits to research participants. When conducting research with children, the minimal risk threshold is applied unless the research is expected to be therapeutic. In this case, a minor increase over minimal risk may be allowed. Research with healthy children would never involve a therapeutic element (because they are not sick) so any minor increase over minimal risk would not usually be acceptable.
  5. The argument against adaptive design include the potential to undermine the validity and integrity of the research and potentially misuse research money. Pros include using research funds more efficiently and producing research outcomes that may benefit stakeholders and the general public more quickly.
  6. This flexible design can lead to some risks that must be considered, including timing issues (adaptations implemented too early) and insufficiently justified ad hoc changes (Mahajan and Gupta, 2010). It is important to consider how these potential risks may impact the safety of human participants and undercut the integrity/dependability of the research study.

Scenario 3: Testing a New Vaccine

Your research team has developed a vaccine for a communicable disease similar to H1N1 and it has undergone clinical trial testing and evaluation but only in healthy adult populations. You know that one of the groups most seriously impacted during the H1N1 outbreak was pregnant women. You would like to test your drug in pregnant women as soon as possible.

Discussion questions:

  1. Is it fair to recruit pregnant women into this research study? Is it fair to exclude them? Are the risks to research participants, and potential risks to the fetus, worth the benefits to others that may emerge from this study?
  2. What are the consequences of not doing this research with pregnant women?
  3. Do citizens have a duty to participate in research that will potentially only benefit others? Under what circumstances, if any?
  4. Considering unknown risks to the women and the fetus, how would you go about obtaining informed consent from women to participate in this research?

Scenario shift:

You received REB approval to test your vaccine in pregnant women but are having difficulty recruiting participants so your study has stalled. The elderly is another group with high morbidity and mortality from communicable diseases such as the flu and could also benefit from your new vaccine. You think you will have an easier time finding participants in this population because a friend of yours works as a nurse practitioner at a retirement home. She has agreed to help you recruit participants from her facility and explain the risks associated with research participation. For example, it is likely that because of their co-morbidities, the elderly may have a more severe reaction to the vaccine, and there is also greater potential for mortality related to receiving the vaccine.

Additional discussion questions:

  1. How does this case differ from the one that includes pregnant women? Does the harm-benefit balance shift?
  2. How would you go about obtaining informed consent for the elderly to participate in this research? What are the special considerations in obtaining consent from this group? Is it acceptable to recruit participants from a retirement home?

Relevant ethics guidance documents:

Links to the Ethics Cycle conceptual framework:

  • Through this scenario, participants can address issues under the following topics:
    • Assess barriers to use (results must be translated to groups equitably, all should have fair access) (KT).
    • Towards next generation research (the research conducted (or not conducted) today will inform future research efforts) (KT).
    • Toward continued KT (resources including knowledge must be fairly allocated) (KT).
    • Analyze data (recruit participants-the recruitment of participants impacts how data can be analyzed as well as applied) (KC).
    • Further research (how research is framed impacts future research that is built on current results) (KC).
    • Draw conclusions (researchers should be aware of how the conclusions of their studies impacts individuals and groups) (KC).

Link to real life case study:

Discussion Guide:

  1. Harms and benefits to research participants (including the ways in which the vaccine may be beneficial to fetal health) as well as harms and benefits to the broader community they represent (i.e., all pregnant women) should be discussed. Autonomy (respecting an individual’s right to choose) should also be taken into account.
  2. Consequences include: not being exposed to the risks of the research; not gaining an understanding of the risks to developing fetuses; and not being able to benefit from research results (i.e., through a vaccine).
  3. Consider issues of autonomy (including informed consent) versus social justice and responsibilities and duties we have as citizens. What are these duties? What would happen if everyone refused to participate in research?
  4. Discuss components of the consent process such as: the meaning of free and informed consent; how to present possible risks and benefits; etc.
  5. Risks of death/harms may differ. Broader justice/social implications and acceptable levels of risk to certain segments of the population may also be considered, including the potential for coercion among certain groups. For example, do potential participants really feel they can say ‘no’ to those who are providing their care? Are we taking advantage of a trusted relationship?
  6. Consider the components of consent including whether it is free (e.g., not coerced) and informed (e.g., capacity issues and the use of substitute decision-makers). What makes a retirement home a “special case”? How is it different from recruiting elderly people from a mall or community center? How would you feel if this was your grandma’s nursing home?

Footnotes

Footnote 1

Adaptive design can be described as “a study that includes a prospectively planned opportunity for modification of one or more specified aspects of the study design and hypotheses based on analysis of data (usually interim data) from subjects in the study”. Mahajan, R. and Gupta, K. (2010). Adaptive design clinical trials: Methodology, challenges and prospect. Indian Journal of Pharmacology 42(4): 201–207.

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