The end of the year rush to approve drugs has unintended negative consequences for patients, according to an HBS, MIT and University of Texas, Dallas, study.
Allie Nawrat investigates the reasons behind this pattern and talks to co-author HBS professor Lauren Cohen about how it could be resolved.
Medical regulators around the world approve more drugs in December than any other time of the year. Based on qualitative analysis of application and approval data from the US, the European Union (EU), Japan, China and South Korea, as well as public records of adverse event reporting to healthcare professionals, US-based researchers discovered a worrying trend linked with this state of affairs.
Despite not sharing figures, the Harvard Business School (HBS), the University of Texas, Dallas, and the Massachusetts Institute of Technology (MIT) study found that these so-called ‘December drugs’ are often rushed through the approval processes, and are related to significantly more adverse events, ranging from hospitalisation to death. In fact, the study found the drugs with the hastiest review were associated with the most adverse events.
This situation is at complete odds with the core mission of regulators being to ensure drugs on the market are safe and effective for at-need patients.
Rather than focusing on the precise number of drugs approved, the primary aim of the research was to try and establish the reasons and psychology behind this end of year approval trend. One of the authors HBS L E Simmons professor of business administration Lauren Cohen explains: “there are no explicit quotas for any of these drugs approval agencies for the number of drugs they need to approve of any given year, nor are their fiscal year ends at year-end for each of these organisations.” For example, the US Food and Drug’s Administration’s fiscal year ends in September, so you would expect a US spike in September instead of January.
If this pattern cannot be explained by formal, explicit targets and deadlines, what explains this so-called December drugs rush?
Psychology of drug regulators
Cohen and his co-authors conclude this pattern is caused by “desk clearing behaviour”, rather than explicit deadlines and targets set by the regulators themselves. “These psychological quotas have been shown in other contexts to impact on behaviour,” Cohen notes.
He explains there are “salient psychological benefits” of starting a new year without a significant backlog of work.
To confirm the desk clearing hypothesis, and rule out other possibilities, the researchers controlled for the drug’s indication, market size and priority review status to ensure regulators were not reserving the most complex drugs to approve at the end of the year.
They also found that the drugs approved in December did not seem to be more difficult to review and there was no evidence that companies strategically timed their review timing to get a rushed December review, which is more likely to lead to approval than rejection.
This conclusion was further augmented by the study’s observation that similar spikes were found at month ends and before important national holidays – such as Thanksgiving in the US and Lunar New Year in China.
Examining this phenomenon in multiple global jurisdictions is what differs this HBS, University of Texas and MIT report from previous work by professor Daniel Carpenter and others; the fact this pattern is global further proves the December drugs phenomenon is not an inadequacy of the US FDA’s review approach.
Importantly, this aspect of the study “gave us the ability to study the impact of national holidays” on desk clearing behaviour, Cohen explains. “Thanksgiving is only celebrated in the US, and we see a spike in drug approvals in the US, but nowhere else. [Whereas] in China, we see a spike before Lunar New Year, but not in the US.”
Interestingly, the fact that Cohen and his research partners found that “drugs rushed through the most seem to be the ones where adverse effect consequences are concentrated” further suggests it is this hasty desk clearing psychology that causes low-quality reviews of drugs and the associated adverse events.
Erring towards approval
Another part of the explanation is there a pressure on regulators to approve drugs, rather than reject them. The researchers explain the default stance of regulators is to approve drugs; although employees do not receive bonuses, promotions or other explicit incentives for approving a certain number of drugs, informal performance benchmarks focus on the number of drugs approved, rather than the quality of the decision.
This is because approval is a more salient marker of success than adverse events, particularly since the downsides of drug approvals can take years to be realised and revealed. Cohen notes there is an “asymmetry between approval and rejection” because “you can’t run that counterfactual check” saying look how many hospitalisations and deaths we avoided by not approving, Cohen notes; meaning there are ”no explicit incentives for making the right decision” about a drug.
Looking externally, there are a number of stakeholders pushing for drug approvals, ranging from companies to patients, whereas very few people are seeking rejections. Further to this, drug regulators are compared based on measurable approval output.
In addition, Cohen explains the FDA, for instance, uses the number of drug approvals in a year as evidence of productivity and justify a continuation or increase of their budget to Congress. However, it is much harder to make the same arguments based on a hypothetical estimate of the regulator foreseeing the negative impact a drug might have had and therefore rejecting it.
Protecting patients: the need for re-review
Since desk clearing puts patients’ lives at risk, Cohen notes that drugs that are rushed through at the end of a month or end of the year or before a holiday and part of a desk clearing phenomenon should be scrutinised a bit more.
The report calls for ‘December drugs’, as well as those approved at the end of months and before holidays, to be re-reviewed by regulators to make sure nothing concerning was overlooked in the initial approach. Cohen states: “I think a quick review would do wonders…especially given that we found the drugs rushed the most were the ones with the most adverse events in the future.”
Another way to place a spotlight on the potential negative consequences of drugs following rushed approvals is through the collection and analysis of real-world data to better monitor adverse events of drugs that went through a rushed approval.
By Allie Nawrat
Source: Pharmaceutical Technology
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