Orphan Drug Development
Clinical trials conducted on any rare diseases that are intended for the marketing and approval of a new drug candidate for the purpose of establishing future novel therapy is known as orphan drug development. Orphan drugs trials are always of high importance in scientific community as these are tough to conduct in terms of regulation, Pharmacoeconomics, trials design and implementation. Since there are only a very few rare diseases trials being conducted, all the stakeholders intend to squeeze out maximum benefits from the trial.
As per the United States foods, drugs and cosmetic acts, rare diseases are such disease or conditions which impacts less than 200,000 peoples residing in the United States. Similarly, in European Union, a disease is considered to be rare if it affects one person out of 2000 citizens. There have been more than 6000 rare disease discovered so far affecting approximately around 3.5 to 5.9 % of worlds population. Most of rare disease have genetic origin (72%) and hence are difficult to treat with medication.
Why Clinical trials on rare disease is difficult?
1. Understanding Disease mechanics : There is very little understanding of disease mechanisms and pathophysiology of any rare disease which makes it impossible for a new therapy to establish inference on intervention and the outcome.
2. Genetic Variability: Since majority of rare disease have genetic predisposition, clinical manifestation for each of them will be different and drug effective for one type of genetic makeup may not be the best option for another group with different genetics. This specially makes clinical trials more complicated.
3. Too less events: Though significant number of people are affected with various rare disease throughout the world, there are too few people available for a single clinical trial as the patient pool for each diseases under trial is always lesser than required for the enrollment.
4. Adolescent predominance: Since most of the rare diseases are manifestoed in early childhood and adolescence, it is difficult to conduct trial on children and people with younger age due to legal and ethical issues. Also the rate of compliance to the clinical trial protocol is still very low.
5. Statistical Insufficiency: Currently applied outcome measures are not appropriate for rare disease and reliability of newer methods is ambiguous. For example, smaller effect size etc.
6. Pharmacoeconomic Reasons: Since clinical trials are very costly, if return on investment for any trial is seemingly low, pharmaceutical industry is less likely to invest their money for the good of society and science only. In comparison to other conventional trials and their outcome in the world, conducting clinical trials with inherently very low success rate is nto good idea for commercially oriented pharmaceutical companies and considering their return on investment, it is less likely to invest.
Current number on Rare Diseases Trials
While putting keyword 'Rare Disease Trials', a total of 564 studies are popped out in clinicaltrials.gov, , out of which only 91 studies are currently recruiting participants whereas 342 have been already completed. Rest of the studies are either 'not yet recruiting' or ' suspended' from the process.
Opportunities and Way Forward
1. Noncommercial research activities. Unlike other clinical trials on a pharmaceutical product, there are very limited chances of trials getting successful on receiving license for market, sponsors may not be much interested taking such a challenge. Only a researcher organization with multiple collaboration should conduct such trials overlooking cost - benefit analysis of such research projects.
2. Lenient regulatory obligations: if we apply the same regulatory framework with similar degree of scrutiny in rare diseases trial as we don in other exploratory / pragmatic clinical trials, there are chances of any such trial not to meet regulatory requirements. Hence, right from the pre trial implementation documents, rare disease trials should are conducted with much less of scrutiny and legal system are made easier so that such studies are promoted in the scientific era as well.
