This is sometimes referred to as the Streetlight Effect – a phenomenon aptly illustrated by Mutt and Jeff over half a century ago:
This is the situation that the Tufts Center for the Study of Drug Development seems to have gotten itself into in its latest "Impact Report". It’s worth walking through the process of how an interesting question ends up in an uninteresting answer.
So, here’s an interesting question:
My company owns a drug that may be approvable through FDA’s 505(b)(2) pathway. What is the estimated time and cost difference between pursuing 505(b)(2) approval and conventional approval?That’s "interesting", I suppose I should add, for a certain subset of folks working in drug development and commercialization. It’s only interesting to that peculiar niche, but for those people I suspect it’s extremely interesting - because it is a real situation that a drug company may find itself in, and there are concrete consequences to the decision.
Unfortunately, this is also a really difficult question to answer. As phrased, you'd almost need a randomized trial to answer it. Let’s create a version which is less interesting but easier to answer:
What are the overall development time and cost differences between drugs seeking approval via 505(b)(2) and conventional pathways?This is much easier to answer, as pharmaceutical companies could look back on development times and costs of all their compounds, and directly compare the different types. It is, however, a much less useful question. Many new drugs are simply not eligible for 505(b)(2) approval. If those drugs
|Extreme qualitative differences of 505(b)(2) drugs. |
Source: Thomson Reuters analysis via RAPS
So we’re likely to get a lot of confounding factors in our comparison, and it’s unclear how the answer would (or should) guide us if we were truly trying to decide which route to take for a particular new drug. It might help us if we were trying to evaluate a large-scale shift to prioritizing 505(b)(2) eligible drugs, however.
Unfortunately, even this question is apparently too difficult to answer. Instead, the Tufts CSDD chose to ask and answer yet another variant:
What is the difference in time that it takes the FDA for its internal review process between 505(b)(2) and conventionally-approved drugs?This question has the supreme virtue of being answerable. In fact, I believe that all of the data you’d need is contained within the approval letter that FDA posts publishes for each new approved drug.
But at the same time, it isn’t a particularly interesting question anymore. The promise of the 505(b)(2) pathway is that it should reduce total development time and cost, but on both those dimensions, the report appears to fall flat.
- Cost: This analysis says nothing about reduced costs – those savings would mostly come in the form of fewer clinical trials, and this focuses entirely on the FDA review process.
- Time: FDA review and approval is only a fraction of a drug’s journey from patent to market. In fact, it often takes up less than 10% of the time from initial IND to approval. So any differences in approval times will likely easily be overshadowed by differences in time spent in development.
The 505(b)(2) approval pathway for new drug applications in the United States, aimed at avoiding unnecessary duplication of studies performed on a previously approved drug, has not led to shorter approval times.This is more than a bit misleading. The 505(b)(2) statute does not in any way address approval timelines – that’s not it’s intent. So showing that it hasn’t led to shorter approval times is less of an insight than it is a natural consequence of the law as written.
Most importantly, showing that 505(b)(2) drugs had a longer average approval time than conventionally-approved drugs in no way should be interpreted as adding any evidence to the idea that those drugs were slowed down by the 505(b)(2) process itself. Because 505(b)(2) drugs are qualitatively different from other new molecules, this study can’t claim that they would have been developed faster had their owners initially chosen to go the route of conventional approval. In fact, such a decision might have resulted in both increased time in trials and increased approval time.
This study simply is not designed to provide an answer to the truly interesting underlying question.
[Disclosure: the above review is based entirely on a CSDD press release and summary page. The actual report costs $125, which is well in excess of this blog’s expense limit. It is entirely possible that the report itself contains more-informative insights, and I’ll happily update that post if that should come to my attention.]