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Ed. note: This is the final post by Dr. Kim Hunter-Schaedle recapping the Conference on Clinical Research for Rare Diseases to see the first post please click here.

A major consideration for a rare disease clinical trial is that it may take a very long time to recruit all of the patients you need. During the time it takes to do a trial, you run the risk of the trial losing momentum; staff turnover, which is inevitable in any clinical research center; or depletion of your own eligible patient population.  This is one reason why rare disease initiatives will often include a number of centers, so that this increases the chances of successful recruitment and advancing the trial more rapidly. However, adding more centers can also dilute out the expertise.

Another implication to be kept in mind from the outset is that if the trial is being supported in full or part by industry, they will have a focus on getting an outcome measure (does drug work or not?) as soon as possible. The funder should be made aware from the outset of the vagaries and potential delays of a rare disease clinical trial. 

Finally - a word about conflicts of interest.  The NIH began regulating conflicts of interest in1995, and federal interest in this area has increased since 2005. For rare diseases, conflicts can arise if an investigator has multiple roles in one trial –such as screening, selection and consenting of patients; and evaluation of data.  In particular evaluating data must be done independently of other trial related activities. Today, most rare disease patients are heavily educated on their condition. Nevertheless, consenting patients for a trial is a complex issue as the clinician often has to go through a fairly complex form with the patient in a limited time frame.

Ed. note: This is the fourth post by Dr. Kim Hunter-Schaedle recapping the Conference on Clinical Research for Rare Diseases to see the first post please click here.

Industry has visibly taken a much greater interest in rare diseases in the recent past, with a few large pharmaceutical companies declaring intent to establish new programs in rare disease. This is in part because for many rare diseases the biology and pathology is now much better known, which will reduce development costs and give companies a more hopeful shot at determining drugs that might act on these diseases. Academic researchers should look to industry to partner with them in rare disease trials, and should aim to secure resources, commitment, expertise and dollars from industry.  In vetting companies for partnership, academic researchers should look for those with an established track record on interest and preferably success in the area of rare diseases.

One of the greatest challenges for rare disease trials is that for many of these conditions, and something on the mind of industry as they approach rare disease, is that there is as yet no defined and widely used standard of care; and this makes it difficult to validate endpoints for interventional clinical trials, and in particular to define anticipated long term outcomes.  Industry recognizes that for chronic rare diseases, a lot of the information that is most useful will probably come from Post Market Analysis (PMA) studies, i.e. those done once the drug is on the marketplace and being widely used over a long period.  Having endpoints that can be used to determine whether or not a drug is effective will be vital in order to get FDA approval. And in diseases with multiple manifestations, which symptoms should be targeted? (in short those that are most severe for the patient).  Looking forward it is anticipated that for many trials surrogate (e.g. biomarker) endpoints may be used; though there may be additional up-front costs involved in order to validate these surrogate endpoint, these will open the way to shorter trials that give an earlier result and cost less.  From an industry perspective, biomarkers are viewed as better than e.g. imaging as endpoints, as they will be easier and cheaper to collect.

One issue that is definitely on the mind of industry is reimbursement and whether a drug will be approved by coverage from insurance.  Interestingly, some international countries are ahead of the US on this, such as the United Kingdom where there is socialized healthcare and the overseeing body, NICE,  determines upfront if a drug will be paid for by insurance or not.  Issues of reimbursement are forefront for industry from the earliest stage of a product’s development.

Next: Considerations for Rare Disease Clinical Trials

For more information visit the Conference website (http://rarediseasesnetwork.epi.usf.edu/conference/index.htm).

Ed. note: This is the third post by Dr. Kim Hunter-Schaedle recapping the Conference on Clinical Research for Rare Diseases to see the first post please click here.

There are many positive aspects to setting up a research consortium. Not least, funding agencies like them, because they usually mean ‘bang for the buck’ - the researchers have already self organized and come up with a collaborative plan.  However setting up a rare disease clinical research consortium presents challenges, especially for running clinical trials. Rare disease clinical trials must be kept small because there will always be a limited access to patients. Despite this one cannot underestimate the cost of a rare disease trial - many of the set up costs for a trial are fixed and must be spent whether the trial includes 100 patients or 1,000. 

There are some practical issues that need to be considered up front. The consortium head must recognize this commitment as a top priority. All sites that participate in the consortium must have a committed team – not just a sole investigator at a site. Participating researchers must recognize that it might take a long time before seeing productivity or success. In terms of publishing results when they do come, senior established investigators should consider the opportunity to give more visibility to junior investigators who are still establishing their careers.

Funding is also a key issue. Although funding is committed for the consortium, the researchers should be on the lookout for additional funding that can be brought in to expand the programs of the consortium. This may be federal, foundation or institutional funding.

Below is a brochure outlining the Foundation's own NF Preclinical Consortium.

Next: A Rare Disease Perspective from Industry

For more information visit the Conference website (http://rarediseasesnetwork.epi.usf.edu/conference/index.htm).