Scurvy was a debilitating ailment that commonly affected sailors in the 18th Century. In 1747, James Lind conducted one of the first ever clinical trials, by giving sailors with scurvy different dietary supplements and documenting the effects on their health. In commemoration of James Lind’s work, International Clinical Trials Day is celebrated on the 20th May each year.
A clinical trial aims to answer a medical question and requires patient participation to do so. The question being asked is usually whether a new treatment – most often a drug – is better than the current gold standard of treatment, although other types of trials, such as observational trials and patient preference trials do take place. If you would like more information about how clinical trials are conducted and specific information about trials currently open to BHD patients, please visit our new Clinical Trials page for patients.
It has been estimated to cost $1 billion to get a drug to market (DiMasi et al., 2003). Although this figure has been called into question by Sir Andrew Witty of GSK, the vast majority of clinical trials are still run by large pharmaceutical companies. Rivalry within the industry has caused a culture of secrecy to prevail and data from clinical trials – particularly negative results – are often not published. This makes it extremely difficult for doctors to make fully informed decisions about which drugs to prescribe their patients. Additionally, the amount of regulatory process and paperwork required to initiate new trials is often a major stumbling block for researchers who are new to the process.
In recent years, calls to make clinical trial data available – such as the Alltrials petition spearheaded by Dr Ben Goldacre, author of Bad Pharma – have been heard by pharmaceutical companies, and a number of companies, including GSK and Roche, have drawn up policies on how they will improve the transparency of clinical data. Furthermore, the Health Research Authority (HRA) – a UK-wide steering committee founded in 2011 – aims to streamline the regulatory process involved with starting a new trial, while maintaining rigour and safety. The HRA has also recently announced plans to collaborate with pharmaceutical companies to improve the transparency of clinical trial data. The increase of freely available data, coupled with reducing the barriers to launching new trials, will hopefully lead to more life-saving treatments becoming available to patients more quickly.
Access to clinical trials is often difficult for patients due to strict eligibility criteria. Additionally, many patient advocate groups feel that they have not been included in the design of clinical trials, both of which may contribute to the fact that nearly a third of clinical trials close early because they cannot enrol enough patients to make the data statistically significant (data presented by Jaime Richardson of Cedars-Sinai Hospital at the Kidney Cancer Association conference, May 2013). If this happens in Phase III, the result is that an effective drug is not approved for general use purely because the trial was badly designed. This was described by Ms Richardson, as “heart-breaking and wasteful.”
In the UK, the Health and Social Care Act of 2012, aims to make access to clinical trials an integral part of patient care pathways within the NHS, which will hopefully increase patient participation in trials. Patient education is also an invaluable part of this process and the need for patient advocate organisations to provide information about clinical trials to their patients is paramount. A number of information resources for both patients and researchers are now available online, and several of these can be found towards the bottom of our new Clinical Trials page.
Recognising the importance of educating patients about clinical trials has led to the development of a number of initiatives to support patients wanting to learn more. For example, Cedars-Sinai Hospital in Los Angeles recently created the role of Clinical Trials Recruitment Navigator, which is currently held by Jaime Richardson. Jaime provides patients with information about appropriate trials, and acts as a point of contact and support for those participating in trials. Meanwhile, in the UK the National Institute for Health Research (NIHR) has launched the “Ok to ask” campaign, which promotes the message that it’s ok for patients to ask their doctor about clinical trials.
However, the above plans and initiatives will be in vain if the public perception of clinical trials is not improved. Currently, many patients are understandably wary of participating in a clinical trial as they are worried about receiving a placebo treatment, or that they will be treated as a guinea-pig. Additionally, clinical trials are seen by many as a last resort; only to be considered once all other lines of treatment have failed. In reality, clinical trials are sometimes the only way to access the best drugs and because patients are monitored so closely during the trial, they often receive a better standard of care. Placebo treatments in clinical trials are increasingly rare, and are never used in cancer clinical trials, due to the ethical implications of giving someone who is ill a fake treatment. Contrary to the opinion that clinical trials are a last resort, instead they should be considered as another treatment option upon diagnosis: prior treatment can often make a patient ineligible for a clinical trial, whereas if the clinical trial drug proves ineffective, it is always possible to leave the trial and start traditional treatments before the disease has progressed.
The only trials open to BHD patients at present are observational (details can be found at the bottom of our Clinical Trials page). As BHD is a rare disease, there is currently relatively little data to accurately determine the chances of an individual with a FLCN mutation developing skin lesions, pulmonary cysts, or kidney cancer. As previously discussed, determining this epidemiological data accurately would be a great help in being able to advise newly diagnosed patients of their likely disease progression. There are also several other symptoms, such as parotid lesions and colon cancer, which may be associated with BHD but cannot be conclusively proven at this stage. Observational trials may allow clinicians to conclusively determine whether these symptoms are a risk in BHD syndrome.
Looking to the future, as the profile of rare diseases is raised within the research and pharmaceutical communities, more clinical trials testing potential cures for rare diseases are likely to be launched. The role of patient advocate groups will prove fundamental to this process, as in the case of the Multicenter International LAM Efficacy of Sirolimus (MILES) trial (McCormack et al., 2011) for which The LAM Foundation’s involvement was pivotal in recruiting patients.
Of course, participation in a trial must always be the patient’s decision, but the choice to not participate must be due to “informed refusal” rather than to a lack of access or information. The reasons for participation – or not – are complicated, visceral and utterly personal, and rightly so. But it is always worth bearing in mind that today’s drugs were yesterday’s clinical trials; were it not for James Lind’s efforts in 1747, we wouldn’t know that citrus fruits are a cheap and effective cure for scurvy.
- DiMasi JA, Hansen RW, & Grabowski HG (2003). The price of innovation: new estimates of drug development costs. Journal of health economics, 22 (2), 151-85 PMID: 12606142
- McCormack FX, Inoue Y, Moss J, Singer LG, Strange C, Nakata K, Barker AF, Chapman JT, Brantly ML, Stocks JM, Brown KK, Lynch JP 3rd, Goldberg HJ, Young LR, Kinder BW, Downey GP, Sullivan EJ, Colby TV, McKay RT, Cohen MM, Korbee L, Taveira-DaSilva AM, Lee HS, Krischer JP, Trapnell BC, National Institutes of Health Rare Lung Diseases Consortium, & MILES Trial Group (2011). Efficacy and safety of sirolimus in lymphangioleiomyomatosis. The New England journal of medicine, 364 (17), 1595-606 PMID: 21410393
www.bhdsyndrome.org – the primary online resource for anyone interested in BHD Syndrome.