Clinical Cataloguing: Processing the Kennedy Trust for Rheumatology Research Archive
Clinical study records are central to the The Kennedy Trust Archive and what it contains. This post introduces the archive and explains how archivist Annie Lord sought to portray the complexity of the collection, to find ways for patient voices to be heard, and to make the collection more accessible to a wider range of researchers.
In 2022, I began a 12-month role at Wellcome Collection to catalogue the Kennedy Trust for Rheumatology Research archive. The collection largely relates to the ground-breaking discovery and development of anti-TNF drugs for rheumatoid arthritis that took place between the 1980s and early 2000s. The collection contains records relating to the involvement of the Kennedy Trust in anti-TNF drug development, records relating to the history, governance and administration of the Kennedy Trust, and some papers of renowned scientists Sir Marc Feldmann and Sir Ravinder Maini. Clinical study records are central to the The Kennedy Trust Archive and what it contains. In this post I will introduce the archive and explain how I have sought to portray the complexity of the collection, to find ways for patient voices to be heard, and to make the collection more accessible to a wider range of researchers.
What is Rheumatoid Arthritis?
Rheumatoid arthritis or RA is an autoimmune disease which predominately causes inflammation, erosion, and pain of the joints. Around 400,000 adults aged over 16 in the UK are currently affected by RA. It can affect anyone at any age. Symptoms are not limited to joint pain and can involve fatigue, weight-loss and chest pain. The condition can impact every day activities including dressing, preparing food and working. Those with RA also face the challenge of getting a diagnosis, finding the right treatment and challenging the misconceptions around the disease. Both the physical and emotional challenges associated with RA can influence a person’s quality of life, leading to low mood and mental health conditions.
Historic Rheumatoid Arthritis and Treatment
While it is not possible to know at what exact point in history rheumatoid arthritis started to occur, the work and legacies of influential individuals allow us to place RA in the last 400 years.
Peter Paul Rubens (1577–1640)- a Flemish artist whose paintings are argued to depict RA. His death of gout in 1640 has raised questions over whether he himself suffered from RA in the final decades of his life.
Pierre-Auguste Renoir (1841–1919)- the famous French painter is known to have developed RA in his 50s. It is alleged he even strapped his brushes to his hands to be able to paint despite his significant joint deformity.
Dorothy Hodgkin (1910–1994)- Nobel Prize winning scientist who developed RA in her 20s. Hodgkin is best known for the development of protein crystallography and determining the structure of Penicillin, vitamin B12 and insulin. Her most remarkable contributions to science came post RA diagnosis, despite living with significant pain and progressive joint destruction.
Throughout history many treatments for RA have been tried and tested leading to today’s common use of biological treatments. These include:
Natural remedies for inflammation such as willow bark and juniper berries (c.17th century-present day)
Metals including copper, brass, steel, and zinc (c.19th century-present day)
Pain killers and non-steroidal anti-inflammatory drugs NSAIDs i.e. Aspirin and Ibuprofen (1897-present day)
Gold treatment/injections (c.1920–1980s)
Surgical joint replacement (c.1960s-present day)
Steroids (1950-present day)
Disease modifying anti-rheumatic drugs including methotrexate DMARDs (1980s-present day)
Biological treatments (anti-TNF) including infliximab (1990s-present day)
Who Are The Kennedy Trust for Rheumatology Research?
The Kennedy Trust for Rheumatology Research (formerly the Kennedy Institute of Rheumatology) was founded in 1965. The Kennedy Institute (originally located in Hammersmith) was the first institute in the world concentrating entirely on scientific research into all aspects of rheumatic disease. The creation of the Institute was made possible by a foundation gift of £500,000 to the Charing Cross Hospital Group from the Mathilda and Terence Kennedy Charitable Trust. Mathilda Kennedy was the daughter of Michael Marks, the founder of Marks and Spencer, and Terrence Kennedy was an American writer who married Mathilda in 1950. After seeing their general practitioner Dr Leslie Lankester struggle to find the right treatment for rheumatoid arthritis, the couple were motivated to contribute to finding a cure for the disease. Alongside the Kennedy grant, an additional grant of £200,000 to create the Institute was given by the Arthritis and Rheumatism Council for Research (now Versus Arthritis). Princess Margaret was a patron of the Institute and made regular visits to the Trust after it opened in 1965.
In the 1980s the Kennedy Institute supported research into the disease mechanisms of rheumatoid arthritis, which led to the pioneering development of anti-TNF drugs. In 2000 the Institute and the Trust separated and in 2011 the Kennedy Institute became part of the University of Oxford. Today the Kennedy Trust continues to fund research into the development of cures and preventative treatment for musculoskeletal and related inflammatory diseases. In 2019 the Kennedy Trust loaned their anti-TNF related archive to Wellcome Collection and the work to catalogue the collection started in June 2022.
What is Anti-TNF?
The Kennedy Trust archive largely centres on the discovery and development of anti-TNF treatment for Rheumatoid Arthritis. Anti-TNF is a biological therapy (a treatment made in living cells) that targets a protein called TNF (tumor necrosis factor) which is found in high quantities in the bodies of people with rheumatoid arthritis. The overproduction of TNF causes inflammation, pain, and the destruction of joints. When administered via injection (under the skin or into a vein) anti-TNF antibodies target and bind to the TNF proteins to block the TNF protein from attaching to immune cells in the joints, preventing build up of inflammation. Watch this video by Versus Arthritis for an explanation of how anti-TNF works.
In the 1980s research breakthroughs by Kennedy Institute scientists including Fionula Brennan, Marc Feldmann and Ravinder Maini, started a journey to develop anti-TNF drugs. The anti-TNF drug developed by the Kennedy Institute, pharmaceutical sponsors and research partners was called Infliximab or Remicade. It is a long-term treatment given via an infusion every 8 weeks. The early clinical trials to test anti-TNF proved very successful (as is evidenced in the archive) and it is now common to take a combination of anti-TNF therapy alongside traditional drugs such as methotrexate as a means of managing symptoms. Anti-TNF is also now used to treat other autoimmune diseases such as ankylosing spondylitis, Chrons disease and ulcerative colitis. By 2014 there were five anti-TNF drugs in clinical use and three of the five top-selling drugs in the world were anti-TNF.
Despite the obvious success of the drug, anti-TNF treatment does not work for everyone. It is expensive, it can have side effects and it makes people immune-suppressed, which when reflecting on the ongoing COVID-19 pandemic is a worrying side effect of treatment for many. Thus, ongoing research into RA is vital to developing future treatment.
Describing Clinical Studies Within the Archive Collection
When I began this role and started delving into the collection I was struck by the clinical, scientific, and legal language used in the records. As a cataloguing archivist I can adapt to varied collections, topics, and points in history. However, after opening the first few boxes of the collection and spending time googling antibodies, proteins, cells, biologics and various other scientific terms, I questioned how I could portray the complexity of the collection, whilst not creating barriers for a wide range of researchers. I looked to other archival catalogues held at Wellcome Collection to seek guidance on cataloguing clinical studies in particular. However, whilst I found examples of clinical trials or studies as items within collections, the Kennedy Trust Archive appears to be the only collection where the clinical study records are central to the collection and what it contains. Therefore it has been important for me to create a standard of describing clinical studies in an accessible way.
Thinking carefully about when or how to use certain scientific terms within the catalogue record is one area I have identified to enable descriptions to be more accessible. For instance, the first section of the collection I catalogued was the Kennedy Trust led clinical studies. The records detail anti-TNF drug development between 1991–2006 and feature protocols, ethical correspondence, X-rays, patient files and study data/findings. Rather than using the language found in the scientific protocols to describe the study, I lifted alternative language and explanations from the patient information sheets (significantly more digestible documents) as guides for clinical study descriptions.
Example: T07 Clinical Study description (SA/KET/A/1/2)
The study was conducted by the Kennedy Institute for Rheumatology, led by investigators Prof. Ravinder Maini and Prof. Marc Feldmann and sponsored by the pharmaceutical company Centocor. The aim of the study was to investigate the safety and the therapeutic effect of an chimeric anti-TNF antibody (code name cA2) in patients with rheumatoid arthritis. 20 patients were involved in the study which lasted eight weeks from the first infusion. The results of the study were encouraging, leading to further clinical studies/trials and the development of anti-TNF drugs.
Similarly, I have expanded on my own research process of understanding the scientific and medical jargon contained in the collection by creating a terminology resource (or collection glossary). I aim to link the glossary to the archive at collection level or include in the collection file as an additional resource for researchers to use alongside the catalogue. I hope to implement this when the public facing catalogue goes live at the end of the project in June 2023.
Examples from the glossary:
Ankylosing spondylitis: (AS) is a type of arthritis that mainly affects the back, by causing inflammation in the spine. This can make your back, rib cage and neck stiff and painful.
Cytokines: Are small proteins that are crucial in controlling the growth and activity of other immune system cells and blood cells. When released, they signal the immune system to do its job. Cytokines affect the growth of all blood cells and other cells that help the body’s immune and inflammation responses.
MREC: Multi-centre Research Ethics Committees. The role of the MREC is to ensure a clinical study and its protocol is scientifically valid and ethical.
The collection glossary covers medical terms, and medical conditions, as well as administrative language used in clinical trials. My hope is that the creation of this resource (alongside traditional archival cataloguing) will facilitate research and serve to make our collections more accessible and useable for a wider range of researchers.
Engaging Audiences Using a Clinical Collection
Whilst the Kennedy Trust archive offers the perspective of scientists and the pharmaceutical collaborators connected to the development of anti-TNF, there is limited evidence of patient experience in the archive. The area of the collection containing the most insight of lived RA experience is in the clinical study patient files, trial follow up questionnaires and elements of the ethical correspondence.
Example: Extracts of patient follow up questionnaires (SA/KET/A/1/13)
Question: We are unable to offer further treatment with Anti-TNFa as it is still unlicensed. However, if you could have further treatment would you want to…?
Answer: Without hesitation yes!! (Please!) Can I be the first?
Question: Compared to other treatments you have received for your arthritis was Anti-TNFa a) the best b) about the same c) worse?
Answer: The best
Question: Why?
Answer: Relief from pain, stiffness and depression
Records like this go some way in demonstrating the impact of anti-TNF through the lens of the patient. However, many patient led records in the collection (including the above example) contain personal and special category health data that cannot be anonymised in a research setting. If used, this data could create significant risks to the individual’s fundamental rights and freedoms. Therefore, in order to comply with data protection legislation, these records will be closed for the lifetime of the patient and potentially restricted thereafter in order to protect the patient’s family.
In response to the closure of most patient records, I am seeking alternative ways to access and document a patient-centred experience of the Anti-TNF story to supplement the clinical story. I have started working with the charity Versus Arthritis (VA) who are historically involved in the funding and development of anti-TNF. The charity is a hub of resource, support, and community to many living with rheumatoid arthritis. Therefore, working with VA is an opportunity to explore how we can connect those living with inflammatory disease to the archive collection. Whether through oral history, workshops, articles, or social media, together we are exploring how to best represent, preserve and engage with the voices of those who have experienced anti-TNF treatment both good, bad and everything in between. Stay tuned for the results of this collaboration and work!
Final Thoughts
The Kennedy Trust archive offers a comprehensive understanding of the recent history and breakthroughs in inflammatory disease and rheumatoid arthritis. It also provides a unique insight into the process of creating, testing, patenting a drug and profiting from it’s invention. Based on my conversations with the Kennedy Trust, Versus Arthritis and colleagues in Collections and Research, the clinical contents of the collection will be of significant value to scientists and related researchers looking into the history of RA treatment. However, I hope I have demonstrated how I am also considering a wider research audience for this collection (such as those currently living with RA) by integrating further cataloguing and engagement considerations into the business-as-usual working process for a cataloguing archivist in Collections Information.
Related Resources
Information on Rheumatoid Arthritis and inflammatory disease Versus Arthritis.
History of the Kennedy Trust.
Remicade Drug Information.
Wellcome Collection Kennedy Trust archive interim description.
