Clinical trials can be extremely lengthly and there have been many discussions about how to get medicines to patients more efficiently than the seemingly bureaucratic process that is currently in place.
Real-Time Oncology Review Pilot Program is a project to try and reduce the time needed to gain approval.
There are important caveats though.
Submissions to be considered for the RTOR pilot should meet the following criteria:
Drugs likely to demonstrate substantial improvements over available therapy, which may include drugs previously granted Breakthrough Therapy Designation for the same or other indications. Drugs meeting other criteria for other expedited programs (e.g. fast track, priority review) may also be considered. Straight forward study designs, as determined by the review division and the OCE. Studies conducted exclusively outside the United States and adjuvant, neoadjuvant, and prevention studies will be excluded. Endpoints that can be easily interpreted (for example, overall survival in a randomized trial). Supplements with CMC formulation changes and supplements with pharmacology/toxicology data will be excluded. Submissions with greater complexity, including those with companion diagnostics, may also be excluded for the purposes of the pilot program.
The real time review means the FDA can continuously review data as it is produced and give early feedback.
RTOR allows the FDA to review much of the data earlier, before the applicant formally submits the complete application. First, the applicant will present topline data for the FDA to determine whether RTOR would be appropriate for the supplement. If the agency determines RTOR is an appropriate review pathway, the applicant can start sending pre-submission data to the agency, under the original NDA/BLA, 2-4 weeks after all patient data has been entered and locked by the applicant in their database
This sort of process may be ideal for some indications where the trials give clear end points, survival in oncology, clearance of parasite in Malaria or other infectious diseases. Clinical trials for Psychiatric disease, marginal improvements over existing therapy or slowly progressing neurological diseases will probably not be suitable.
An interesting publication in PLOS Medicine titled “Why Most Clinical Research Is Not Useful” DOI.
John P. A. Ioannidis suggests that a series of features that make clinical research useful can be identified, including those relating to problem base, context placement, information gain, pragmatism, patient centeredness, value for money, feasibility, and transparency and concludes …
Overall, not only are (clinical) most research findings false, but, furthermore, most of the true findings are not useful. Medical interventions should and can result in huge human benefit. It makes no sense to perform clinical research without ensuring clinical utility. Reform and improvement are overdue.
Given the costs involved I suspect this final point may catch the eye.
Reform is needed. Altering our approach could easily produce more clinical research that is useful, at the same or even at a massively reduced cost
Biotechnology Innovation Organisation (BIO) have released the results of a huge study on clinical development success rates.
The study included 9,985 clinical trails and covered a wide number of therapeutic ares including Allergy, Autoimmune, Cardiovascular, Chronic High Prevalence Diseases, Endocrine, Gastroenterology, Hematology, Infectious Disease, Metabolic, Neurology, Oncology, Ophthalmology, Psychiatry, Rare Diseases, Respirator, and Urology.
Key findings from the study include:
- Clinical trial programs that used selection biomarkers saw an overall likelihood of approval (LOA) from Phase I of 25.9%, compared to 8.4% when no selection biomarkers were used.
- The overall LOA from Phase I for all developmental candidates was 9.6%, and 11.9% for all indications outside of Oncology.
- Of the 14 major disease areas studied, Hematology had the highest LOA from Phase I (26.1%) and Oncology had the lowest (5.1%).
- Oncology drugs were approved the fastest of all 14 disease areas.
- Rare disease programs had higher success rates at each phase of development vs. the overall dataset.
- Chronic diseases with high populations had lower LOA from Phase I vs. the overall dataset.
- Phase II clinical programs continue to experience the lowest success rate of the four development phases, with only 30.7% of developmental candidates advancing to Phase III
A great detective story and also serves to underline the need for all clinical trial data to be published and stored in a publicly accessible format.
Ramsden, of the National Institutes of Health, unearthed raw data from a 40-year-old study, which challenges the dogma that eating vegetable fats instead of animal fats is good for the heart. The study, the largest gold-standard experiment testing that idea, found the opposite, Ramsden and his colleagues reported on Tuesday in BMJ.