The Life of a Drug After Clinical Trials
During the development of a new drug, the primary focus is on assessing whether it’s safe (i.e., the benefit to the patient outweighs the impact of the side effects) and whether it works (Explanatory Trial/ Study). In order to answer these questions, it’s important to remove as many variables as possible, which means testing on patients who have as few as possible medical conditions, other than the one being investigated, and who are taking a minimal number of other drugs (i.e., concomitant medications).
However, the drug will be used on ‘real people’, which usually means we have a multitude of medical conditions (that seem to grow exponentially as we grow older) and we are taking a variety of drugs in order to combat these conditions and the side effects of the drugs. There are also the over the counter (OTC) drugs that we use when needed, such as painkillers, anti-histamines, hang-over cures etc.
The drug wasn’t tested in all these ‘real world’ scenarios, to do so would be impractical.
The Need for ‘Real World Evidence’
There is a significant knowledge gap regarding the benefit of these drugs once they have been approved.
We need to know whether these drugs work as well in the real world as they did in clinical trials and whether there are new side effects/ adverse reactions that were not seen previously. We also need to know whether the new drug is better/ more beneficial than drugs already on the market, whether it’s used properly by the prescribing doctors and the patients (i.e. as per the instructions provided in the drug label). Obviously, I’m over-simplifying things here, but you get the message.
So how do we get this information/ fill this knowledge gap?
We assess the use of these drugs in situations identical to, or close to, routine clinical practice. These assessments can either be interventional (e.g., we dictate which patients receive which drug in a research protocol, but the drug is still used according to it’s authorized purpose) or non-interventional (i.e., the patient is already receiving the drug and we collect information on how it’s being used, how well it’s working, and what side effects/ adverse reactions the patient experiences).
What are Pragmatic Clinical Trials?
According to Wichler et al., (2015), pragmatic clinical trials (PCTs) are randomized trials that seek to compare the effectiveness of two or more interventions in real-world settings. Generally, PCTs are closely integrated with clinical practice, incorporate outcomes that are relevant to patients and other relevant stakeholders, include a broad range of clinical settings, and have minimal exclusion criteria so that the patients reflect those receiving care outside of the trial. These trials seek clinically applicable evidence about the relative advantages and disadvantages of interventions to inform the decisions made by clinicians, patients, and others (Ref: New Definition for a PCT?). Recently, given pressures to improve healthcare quality and interest in transforming healthcare institutions into learning healthcare systems, PCTs have received increased emphasis and support (Whicher et al., 2015).
Purpose of Pragmatic Clinical Trials
Pragmatic clinical trials seek to answer important questions that are applicable to everyday clinical practice (Williams et al., 2015):
- The design of pragmatic trials aims to test an intervention in a study environment that is closer to real life in terms of study population, intervention, comparator, and outcomes.
- Pragmatic trials must still adhere to the stringent trial methods for minimizing selection, performance, information, attrition, selective outcome reporting, and publication bias.
- Pragmatic trials must be prospectively registered and reported fully according to the pragmatic trials extension of the CONSORT statement.
- The PRECIS-2 tool is one method for assessing where on the pragmatic– explanatory continuum a trial resides and which aspects are more pragmatic or explanatory.
- More pragmatic trials should be considered in dermatology so that they better inform patient care
Limitations of Pragmatic Clinical Trials
Williams et al., (2015) list the limitations of pragmatic trials:
- Pragmatic clinical trials can cost more than explanatory trials, and may require a more complex study design.
- The majority of clinical trials are neither entirely pragmatic nor entirely explanatory—they are part of a continuum.
- Pragmatic trials are not suitable for early trials that seek to explore whether a new experimental intervention shows any biological effect.