Implementing Patient-Centric Strategies in a Natural History Trial: A Case Study
Blog by Roberta Alexander, Ph.D.
The San Diego Clinical Research Network (SDCRN) (Clinical Research News, Developments, Resources & More) and the San Diego Chapter of the Association of Clinical Research Professionals (ACRP) (http://www.acrpnet.org/) co-organized an event on June 21st, 2016 at the Scripps Green Hospital in San Diego to discuss patient-centric strategies in clinical research.
The speaker was Jacqui Blem, Senior Director of Clinical Operations at Regulus Therapeutics (http://regulusrx.com/).
Regulus’s technology focuses on microRNA, which are short, non-coding RNA sequences which interfere with RNA translation and, ultimately, regulate protein synthesis. Regulus’s approach aims at modulating the function of microRNAs that are altered in human disease; this technology may be helpful in treating diseases caused by abnormal gene expression. Regulus has several clinical programs in hepatitis C and in Alport Syndrome. Jacqui shared with the audience her experience in conducting a natural history study in Alport syndrome, highlighting the patient-centricity of the study.
What is Alport Syndrome?
Alport Syndrome is an orphan genetic disease affecting approximately 5,000 patients in the USA. Three mutations in the gene that codes for collagen type IV have been identified in these patients. The disease manifests itself at a very early age with kidney disease, hematuria and proteinuria and, eventually, end-stage renal disease (ESRD). Dialysis and kidney transplant are common in Alport Syndrome patients in their 20s and 30s. Hearing loss and eye disease occur early in life as well. The disease is usually diagnosed by pediatric nephrologists; however, diagnosis is difficult – especially if no family history exists – because of the low incidence and slow progression of the disease. Regulus is developing a microRNA therapy for Alport Syndrome, RG012, which gained orphan drug designation by the FDA and the EMeA. Given the rarity of the disease and the paucity of clinical trials, Regulus recognized the importance of better understanding the disease and its progression before testing RG012; this led to the initiation of the natural history study which was the focal point of Jacqui’s talk.
What is a natural history study?
A natural history study, as the name suggests, is designed to study the history of a disease. It is not an interventional study and there is no investigational treatment administered to the patient. Rather, patient visits are conducted to measure clinical parameters and biomarkers over time. The study Regulus is carrying out follows patients with Alport Syndrome every 12 weeks for a period of 2 years; kidney function is measured over time, and biomarkers are measured to better understand the disease and the possible response to therapy.
How do you make this natural history study patient-centric?
Especially when working on orphan diseases, you need to put the patient at the center of your activities, because there are not many patients to begin with. The first hurdle in a study like this is, indeed, patient recruitment. To increase patient participation, Regulus tried to make the study visits as easy as possible for the patient.
Regulus has 15 sites all over the globe to recruit just 150 patients, and is working closely with the Alport Syndrome Foundation to promote awareness via social media and other outlets. Flexibility of diagnosis is important for proper recruitment in an orphan study: although Alport Syndrome is a genetic disease that can be diagnosed with a genetic test, Regulus allows also the inclusion of patients diagnosed clinically or because of disease history. They also offer free genetic testing – which may not be covered by insurance in the USA – to the participants! Although recruitment challenges are to be expected, the global nature of this study posed additional, unexpected, challenges.
Regulus decided to have frequent visits (12 weeks is a short period of time, especially for a slow progressing disease…) and measure glomerular filtration rate, which is a lengthy and cumbersome test: this can be quite an inconvenience for many patients! On the other hand, the 24 hour urine collection turned out not to be a big challenge: patients were given nice insulated backpacks to carry their urine from home to hospital, and they did not mind it!
Because there are only a few specialized centers for Alport Syndrome, in-person visits every 12 weeks are inconvenient, time consuming, and costly for most patients. The cost issue was solved by Regulus reimbursing the patients and their caregivers for travel expenses. Payments and travel arrangements are done by an independent agency to safeguard patient privacy and comply with HIPAA regulations. Different countries have different rules for patient reimbursement, which creates a challenge in a global study; in addition, in some countries, debit cards are widely used, while in others, they are not, adding to the difficulty of the reimbursement program.
To increase compliance and decrease travel, Regulus implemented a home nursing system via a global company. Nurses visit patients at home, perform routine test and physical exams, as well as collect clinical information.
This program did, however, present some challenges. For example, China does not have a home nursing service; thus, Chinese patients need to live relatively close to the site if they wish to participate in the study. In some countries, nurses cannot perform what in the USA is called a physical exam, so the study terminology needed to be changed. In other countries, nurses cannot manipulate dry ice; an arrangement with a courier had to be put in place to circumvent this problem. One key opinion leader did not want their patients to be visited at home by an outside nurse, while a certain hospital wanted to use their own nursing service instead of the global service contracted by Regulus.
Challenges notwithstanding, the study is going well, and the Alport Syndrome patients are excited to participate in a study that furthers the knowledge and understanding of their disease. For us, listening to Jacqui was definitively a great learning experience, and we look forward to the other activities organized by SDCRN and ACRP!