In 2005, Clinical Trials Day was launched to commemorate the anniversary of the first known clinical trial, carried out by Scottish doctor James Lind on board the HMS Salisbury in 1747. By dividing a group of 12 sailors into pairs and allocating them a variety of dietary supplements, he demonstrated that citrus fruits were an effective remedy against scurvy (a disease caused by vitamin C deficiency). This simple study laid the foundation for the modern randomised clinical trial.
Although clinical studies have evolved considerably since the 18th century, their fundamental purpose remains the same: to use a rigorously designed test to give a clear answer to an important question. On Clinical Trials Day 2022, Oxford Population Health researchers share their insights on what makes a good clinical trial.
‘The best trials are collaborations between clinical trialists, medical professionals, and patients, and sharing information freely between them enhances this collaboration. Also, making protocols publicly available can help patients and the scientific community to understand how the trial is operating, and increase their confidence in the results. For the RECOVERY trial, for instance, all the documentation related to the study – including the protocol, correspondence with the data monitoring committee, and results papers – are publicly available on the dedicated website.’
Involving a wide range of people
‘Disease risks can vary for different populations: for instance, Black Americans and Hispanic people have a disproportionately high burden of chronic kidney disease. It is therefore important that clinical trials include a diverse range of participants. The EMPA-KIDNEY trial, for instance, has recruited 6,600 patients with chronic kidney disease across eight different countries. The study has been stopped early due to evidence of a strong benefit, indicating that it could have an important impact for patients of a wide range of ethnicities.’
‘It is important that, wherever possible, clinical trials are designed in ways that make it easy for people to take part, and therefore more accessible. For example, in the LENS trial, we have minimised the number of clinical appointments participants have to attend in-person by mailing the study treatment directly to participants’ homes and conducting the follow-up appointments by telephone. This has allowed the study team to recruit participants from across the whole of mainland Scotland.’
‘Making trials inclusive is absolutely essential to ensure that as many people as possible can benefit from their findings. For example, including pregnant women in the RECOVERY trial means that when we find beneficial treatments for COVID-19, these medications can be used immediately in pregnancy. This is particularly important as we know pregnant women are at greater risk of severe illness.’
Sufficiently long follow-up period
Rosie Bradley, Medical Statistician at Oxford Population Health:
‘Long term follow-up in clinical trials is essential to document side-effects and any harms related to treatments, besides differences in mortality rates which can take a while to become clear. For instance, meta-analyses of breast cancer treatments that we carried out as part of the Early Breast Cancer Trialists’ Collaborative Group found that aromatase inhibitors did not show a survival advantage over tamoxifen after five years, but did so after a longer follow-up period.’
Designed with participants
‘It is so important that clinical trials are shaped by engagement with patients and the public. This ensures that the participant experience is as good as it can be, improves recruitment, and helps to maintain participant engagement throughout. In ASCEND PLUS, for instance, we consulted six patient and public focus groups to inform our recruitment and consent materials, and this feedback was invaluable in making these easier to understand and more inclusive. We have now set up a Public Advisory Group to ensure that every stage of the trial is developed with patient and public guidance.’
Consulting a public advisory group can help those leading clinical trials in various ways, for instance in reviewing information designed for participants
Marian Knight, Professor of Maternal and Child Population Health
‘Trials that make a real difference are those that are well designed and big enough to give a clear answer to a clinically relevant question. For instance, thousands of women die each year from pregnancy-related infections. But the ANODE trial showed that a single dose of antibiotics almost halved the risk of infection for women who had an assisted vaginal birth. As a result, the World Health Organization’s guidance changed, recommending that all women worldwide who have a forceps or vacuum-assisted birth have this single antibiotic dose, thus potentially preventing many thousands of infections.’
Featured clinical trials
- The RECOVERY trial is the world’s largest study of potential treatments for patients hospitalised with severe COVID-19. The study has found four effective treatments so far, and continues to investigate a range of candidate therapies.
- EMPA KIDNEY is testing whether taking a single pill of empagliflozin every day prevents worsening of kidney disease or deaths from heart disease in people who have chronic kidney disease.
- The LENS trial is testing whether taking the cholesterol-lowering drug fenofibrate for four years lowers the risk of worsening diabetic eye disease.
- ASCEND PLUS is investigating whether oral semaglutide can protect against cardiovascular and other outcomes in people with type 2 diabetes and no history of heart attack or stroke.
- The ANODE trial investigated whether a single dose of antibiotic prevented maternal infection after operative vaginal birth.
Find out more in the Guidance for Good Randomized Clinical Trials, produced by the Good Clinical Trials Collaborative.