Clinical trial failure

De Gasperis-Brigante CD, Parker JL, O'Connor PW, Bruno TR. Reducing clinical trial risk in multiple sclerosis. Mult Scler Relat Disord. 2016;5:81-8.

OBJECTIVE:To determine the risk of clinical trial failure for new drugs in multiple sclerosis (MS) and to identify factors that could improve outcomes.
METHODS:We collected data on compounds that were tested in MS from Phase I to Phase III clinical trials between 1998 and January 2015. Clinical trials success rates were calculated and compared to industry standards. The exclusion criteria for the drugs in this study were: drugs that commenced Phase I in MS prior to 1998, non-industry conducted trials, trials testing non-disease modifying drug treatment, and trials testing combinations of drugs already approved by the FDA.
RESULTS: Fifty-three distinct drugs met our inclusion criteria. The cumulative success rate for MS drugs was 27%, almost triple the 10% industry rate. Clinical trial success rates in MS surpass that of industry across all phases. Phase II clinical trials completed in a "Relapsing MS" population were most successful in predicting Phase III clinical trial success. Small molecules were found to have a higher overall success rate compared to biologics; however, both drug technologies largely pursue different molecular targets. Drugs that were previously FDA approved for another indication and were subsequently tested in MS had lower success rates than drugs that had no previous FDA approval history.
CONCLUSIONS: Overall, MS enjoys almost triple the clinical trial success rates of other disease areas. In addition, small molecules are superior to biologics in MS and novel drugs are superior to drugs with a previous FDA approval history outside MS.


As a group that is constantly involved in trials, it is intersting that MS trials are more succssful than other pharma trials in phase I and Phase II. However rather than being happy with 27% success rate of drugs for MS  comparedt o other indications we should be more worried that it is a 73% failure rate. As we have more and more MS drugs hitting the shelves, we know more about DMT that affect relapsing MS the risk of failure due to bad trial design is reduced as the path to the development of an effective DMT is known and  may account for a higher success rate  in MS than other diseases. This is not the case for proggressive MS. where the path to success is still being investigated.  therefore it was not surprising that successful phase II should convert to a successful phase III. Small molecular weight drugs were more effective than biologics and may noy be surprising as biologics generally come with pharmacokinetic and immunogenicity issues, but it was found that new entities where more likely to succeed than repurposed entities.

This comes as little surprise because the repurposed drugs (eg FDA approved for other indications) are not going to have pharma backing and it is sad to say that anything that is not pro pharma and innovative is not going to get a look-in as the powers that be run a mile from this. George Freeman is taking up the rights to prescribe off label but does that mean you can prescribe an expensive alternative off label and does that mean you can devlop an alternative to an  expensive existing pharma drugs....I doubt it, but his true colours need to be exposed. If the drug is not novel who is going to fund development, because it costs so much to do it?

However, maybe we need to to look at the reasons for the 73% failure, is it we are testing rubbish drugs.Is the problem of failure to translate really a problem of animal studies or is it something that clinicans and pharma do.  It is clear that recruitment to studies is a factor. So if  people won't volunteer or volunteer quick enough we never know the answer to some studies.

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