Category: Case studies

bookmark_borderEstimating kidney function: the question of race

Posted on by Gibran Hemani

The issue that we identified

Kidney function was historically assessed using the blood level of serum creatinine, but this had limitations as creatinine in the blood comes from muscle and is therefore determined by more than just kidney function. Two people with the same kidney function will therefore have different creatinine levels in their blood if they have different muscle mass. Factors associated with muscle mass include age, sex, and weight.

Since 1976, equations have been developed to estimate kidney function using blood (serum) creatinine alongside other information about the patient, such as age, sex, body weight. One formula, the MDRD equation developed in 1999 in the United States of America, included African American race as one of its variable, because inclusion of this variable improved the model that estimated kidney function. Later United States and then global guideline bodies then recommended using this equation (and a later adaptation, the CKD-EPI equation) to diagnose chronic kidney disease (CKD) and determine staging.

Initially this use of an African American variable was not challenged, as it is fairly common place in epidemiology to build models using variables that select themselves on the basis of what the add to model performance. However, in 2020 people starting probing into the evidence for its inclusion and questioning a number of assumptions:

  1. The patients included in the studies that were used to develop the MDRD and CKD-EPI equations were from the United States, and Black people in those studies were predominantly from very low socio-economic backgrounds. This raised the possibility that it was not being African American that affected your creatinine generations, but your poverty and perhaps the effect that has on your diet.
  2. There was very little research establishing the link between African American status and creatinine generations
  3. New research in Africa showed that the inclusion of the African American coefficient in the kidney function equations did not improve their accuracy in African populations (and indeed had the opposite effect)
  4. The African American coefficient assumes that all African American are the same (and that all non-African Americans are the same).

By assuming that African American’s generated more creatinine, adjusting for this meant that for the same serum creatinine an African American was estimated to have better kidney function than non-African American with the same serum creatinine. This created a dilemma:

  • If this assumption was incorrect, it was argued that African Americans would be being systematically disadvantaged in terms of timeliness of referral for dialysis or kidney transplantation.
  • If this assumption was correct, however, dropping the African American coefficient would lead to African Americans being labelled with more severe CKD than they actually had, and this might affect access to certain drugs and or insurance.

Actions

In 2021, kidney doctor associations in the United States recommended dropping the African American coefficient from equations estimating kidney function
Shortly after this, researchers in the United States (who had developed the MDRD and CKD-EPI equations) developed a new equation that did not include an African American coefficient.

In the UK, NICE revised its CKD guidance and advised dropping the African American coefficient. Instead, it emphasises the role of clinicians in considering the individual (and their muscle mass) when interpreting serum creatinine and estimated glomerular filtration rate. NICE has not yet advised on use of the new equation.

Impacts

The impact of this change needs to be formally evaluated in research, in particular does it lead to reductions or increases in kidney health inequalities. Efforts are now increasingly going into finding new biomarkers that better estimate kidney function, independent of muscle mass.

What we have learned

The case highlights how a whole global community can accept a research finding and associated guidance without challenging the underlying empirical evidence and assumptions. It also highlights how difficult it can be to know what the right thing to do is, when dropping a race indicator could lead to worsening of kidney health inequalities.

bookmark_borderAncestral diversity in genetic studies

Posted on by Gibran Hemani
  • Course: iBSc Genomic Medicine
  • Unit: Genomic Data Science
  • Authors: Luisa Zuccolo, Kaitlin Wade, Gibran Hemani, Paul Yousefi, Tom Gaunt
  • Contact details: g.hemani@bristol.ac.uk

The issue that we identified

The Genomic Data Science unit teaches students programming and statistical methods for population-scale genetic data. There is a long-standing problem in this field that genetic studies in the vast majority focus on European individuals (https://gwasdiversitymonitor.com/). This is partly due to technical reasons – restricting to a single ancestral group avoids certain statistical problems, but likely also reflects a racial bias that exist more widely in the medical field. Our course material reflected and propagated this bias. The data that we used throughout the course was of European ancestry and, for simplicity, there was no teaching material that described the statistical approaches that would enable our students to handle more diverse genetic data.

The consequences of genetic studies focusing solely on European samples are potentially serious for two reasons. First findings in Europeans may not generalise to more diverse populations, and as a consequence any medical benefits from this work will be restricted to a single ancestral group. Second, more recent statistical techniques that enable the inclusion of diverse samples actually solves a number of problems that can’t be solved when restricting to homogeneous samples.

Our students are the future leaders of this field. We felt it important that they understand the technical reasons for limiting analysis to a single ancestral group, but also learn that including multiple ancestries is not only ethically important but scientifically imperative also.

Actions

We designed a session that asked students to analyse both the merits and pitfalls of restricting genetic analysis to one ancestral group from a purely statistical / technical perspective. Students were asked to form two groups, each tasked with preparing a presentation. The first group would present the statistical benefits of restricting analysis to a single ancestral group; the second group would present the statistical benefits of including multiple ancestral groups in the analysis.

Impacts

We received very positive feedback from the students at the end of the course, in particular for this session. Students appreciated the opportunity to contextualise the technical (and often quite dry) statistical subject matter against the backdrop of social and medical consequences.

What we have learned

During the presentations the students chose to focus more on the sociological impacts than the more technical analytical questions. As a consequence there is a concern that while they appreciate the importance of including diverse samples, they have not necessarily acquired the skills to do this in practice.

A common pitfall relating to decolonisation activities is to simply add a token session at the end of the course that covers the question, which is essentially what has been done here. There does exist an obstacle for us to embed the analysis of diverse samples throughout the course, in that it is substantially more complex than their current materials, and the course is already seen as a substantially complex course. Yet we risk teaching our students out-dated methods by not embracing this added complexity and normalising diversity. This experience has revealed to us that embedding diversity at the core of teaching is important from both an ethical and scientific approach.

bookmark_borderRacial disparities in healthcare conference

Posted on by Gibran Hemani
  • Course: MB21 MB ChB
  • Unit: 3D – Diversity, disability and disadvantage helical theme
  • Authors: Dr Joseph Hartland
  • Contact details: jo.hartland@bristol.ac.uk

The issue that we identified

It was identified by staff and students that although it is important to integrate discussions of race and ethnicity into all of our curriculum there also needed to exist a space where the intersection of race, racism and medicine was discussed specifically. This would allow students to become mor aware of the subject and better employ anti-racist medicine in their studies going forwards.

Actions

As a result we created a day in Year 1 of the MB ChB MB21 course which focused on teaching that explored racism in healthcare and inequalities faced by racially marginalised groups. The purpose of this was to prompt students to reflect on their knowledge of racism, stereotypes and biases they might hold, and to empower the students to be anti-racist in their approach to medicine.

Teaching was delivered by peers from the BAME Medical Student Group and guest lecturers with either lived experience of racism or who are experts in the field of the health inequality explored. This was a mixture of synchronus and asynchronus teaching, supported by a Sway document that can be found here. The timetable for the day with ILOs is available here:

3D-Year-1-Racial-disparties-timetable-links-for-studentsDownload

Impacts

Feedback from students and speakers has been positive. It has created a place early in the curriculum for a difficult subject to be explored by people with the knowledge and understanding to do so. 3rd Sector organisations and people speaking about their lived experience of racism have valued having a platform to speak to students. BAME Medical student group and Year 1 reps were pleased with the content of the day.

What we have learned

The opportunity to frankly raise an important topic and bring in the voices of people seldom heard in society, let alone within medical curriculums.

The day is an intense one, and not all students undertake the asynchronous teaching. Year 1 reps report students struggling with the volume of content in the context of wider curriculum. Spreading the teaching across 2 half days may be more affective.

bookmark_borderIntroducing conversations about difficult subject areas

Posted on by Gibran Hemani
  • Course: iBSc Genomic Medicine
  • Unit: Genomic Data science
  • Authors: Luisa Zuccolo, Kaitlin Wade

The issue that we identified

There is interest and desire from students and lecturers to include decolonisation processes as part of the curriculum, however it can feel like there are barriers to broaching potentially sensitive subjects relating to protected characteristics.

Students and lecturers may be anxious about misspeaking, revealing unconscious biases, causing offense or hurt, or being ‘cancelled’. Students from marginalised groups may feel vulnerable or victimised by these conversations.

How do we create a positive environment for these conversations? How do we encourage engagement from students when anxiety might be heightened?

Actions

We delivered a group presentation / seminar session that analysed the role of inclusion and exclusion of ancestral groups in genetic studies. A number of ground rules were set at the beginning of the session to attempt to set the tone of the conversation and to reduce anxiety about the topic. For example:

  1. Kindness in terms of avoiding intentional hurt or offence
  2. Kindness in terms of accepting each others mistakes
  3. Kindness in terms of pointing out mistakes when necessary
  4. We have a duty to engage
  5. We should treat this as a safe space meaning we do not tolerate violence, harassment or hate speech.

It was acknowledged that this was a new part of the course, the lecturers as well as the students were prone to making mistakes and were keen to learn how to conduct these important discussions in a sensitive and productive way. An excerpt from the session introduction is included below:

Dr Luisa Zuccolo introducing a session discussing ancestry in genetic studies

Impacts

The session did unfold in a very positive and harmonious manner. Students engaged well. Feedback was positive.

What we have learned

There may be value in standardising this way of introducing difficult sessions, e.g. by having a written code that has been crafted by a range of voices, and that can be collectively agreed upon in advance. Other courses and units deal with this same problem routinely and may have established guides on how to create positive environments for difficult conversations.