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Sponsors should use consistent logarithmic adjustments when measuring BE, providing evidence in their clinical trial protocol and statistical analysis plan (SAP) as to why. FDA guidance advises sponsors to log-transform BE measures.
Discover the pivotal role of Bioavailability/Bioequivalence BA BE studies in clinical research with Spinos. As a leading authority in the field, Spinos delves into the nuanced benefits of BA/BE studies, elucidating their profound impact on clinical trials. With a commitment to scientific rigor, Spinos ensures that these studies provide crucial insights into the efficacy and safety of pharmaceutical products.
By meticulously assessing how drugs are absorbed, distributed, and eliminated, Spinos empowers researchers, pharmaceutical companies, and regulatory bodies alike. Uncover the advantages of partnering with Spinos for BA/BE studies, where scientific excellence converges with clinical innovation.
1. Increased Productivity
Clinical trials are one of the main vehicles for translating scientific discoveries to clinical practice, yet despite their importance to our healthcare system they can often be inefficient – diminishing both research quality and outcomes due to outdated trial design techniques or other factors like limited incentives for pharmaceutical companies to create innovative therapies.
At the core of it all lie clinical researchers’ challenges lies subject recruitment. A significant portion of studies that run late are due to being unable to secure enough subjects; this may be caused by overly strict eligibility criteria, unreal trial stipulations or time restrictions.
One potential solution to these issues lies in BA/BE studies. These tests can be used to measure a drug’s bioavailability and bioequivalence, thus ascertaining whether or not the product is safe and effective when taken as prescribed. Testing methods range from dissolution/permeation testing in vitro through to multi-condition approaches with conceptual frameworks for drug absorption.
These methods offer many advantages over conventional in vivo BE, such as providing more focused and relevant data about drug performance in humans than regular BE. Furthermore, they may be more cost-effective; one recent study conservatively estimated that using multi-condition in vitro BE could save one quarter of annual expenditures related to traditional human pharmacokinetic in vivo BE studies.
These BE studies can significantly cut time and costs associated with development while simultaneously increasing trial productivity by freeing up resources that would otherwise be spent conducting in vivo BE studies. It is imperative that new clinical trial designs work hand in hand with regulatory innovations to promote increased productivity both from an R&D viewpoint as well as from an economic one – this latter aspect being essential for mitigating affordability issues and combatting what some have termed the “cost disease” seen within advanced health-care systems.
2. Reduced Time to Market
Conducting BA/BE studies can be time consuming. This is particularly true for drugs undergoing multiple trials to prove regulatory requirements are met and are safe and effective across a range of patient populations. But using cutting edge technologies can significantly cut back this process’ duration, perhaps even eliminating human in vivo BE testing in certain instances altogether.
This is because in vitro testing provides more direct measures of product performance compared to conventional human pharmacokinetic BE in vivo testing. Multi-condition in vitro dissolution and permeation tests with an absorption conceptual framework provide comparable, or better, data than obtained through BE studies.
In vitro testing is far more sensitive to subject-by-formulation interaction effects or highly variable drug references (HVDPs). Conventional in vivo BE tests do not respond as effectively as conventional in vitro BE tests due to their estimation of within-subject variability based on average measurements in each subject.
Therefore, it is crucial that in vitro BE technology be as accurate as possible, including using best permeability practice methods and compendial dissolution equipment. Furthermore, greater insight into type II errors associated with current in vitro BE methods would also prove beneficial; such knowledge could ideally be attained via quality-by-design efforts during product development.
3. Reduced Risk
Clinical trials can be potentially risky and even painful experiences for participants, often causing discomfort or pain during participation. But the greatest danger comes when patients discontinue or fail to adhere with therapeutic plans (this decision might not always be driven by clinical trial data but more by individual beliefs and perceptions about risks associated with each drug (26).
Even though these studies carry inherent risks, all IR solid oral drugs with gastrointestinal tract routes of administration must undergo in vivo BE studies before regulatory approval from the FDA. These studies must show bioequivalence between two competing generic products before being given regulatory approval by regulatory authorities.
Conventional human pharmacokinetic BE in vivo testing typically employs a single dose, two period, two treatment, two sequence open label randomized crossover design to compare plasma profiles of test and reference drugs among fasted, healthy volunteers. However, this can be time consuming and costly as multiple subjects must be included and within-subject variations in Cmax and AUC must be kept to a minimum in order to achieve a Type I error of less than 5%.
Not only can in vivo BE be costly, but other associated costs with conducting clinical trials can be significant as well. Participant recruitment can often prove challenging – particularly when studying chronic conditions or comparative trials with wide indications – and many companies report difficulty sourcing qualified participants willing to join trials with this focus. Recruiting participants also poses unique difficulties within certain disease populations.
Cost and length of clinical trials has put sponsors off from developing new drugs, prompting many pharmaceutical companies to move research efforts outside of the U.S. where clinical trial processes may be more efficient and faster. Furthermore, many physicians lack training in understanding clinical trial results which makes using them in practice and evidence-based medicine difficult.
Effective surrogate endpoints can help lower clinical trial costs by decreasing the frequency and duration of in vivo BE and other human in-human tests that need to be conducted, while adaptive designs can further lower these expenses by shortening study duration and decreasing subject requirements for participation.
4. Increased Productivity
While new technology could eventually bring down pharmaceutical R&D costs, to address the current trend of declining productivity first, clinical trial efficiency must be improved. Increased productivity demands more effective subject recruitment and database use as well as optimizing advertising return – however a significant percentage of trials still miss timelines due to unreachable recruitment targets for subject recruitment targets.
Problems associated with clinical research remain compounded by its site-centricity; schedules largely driven by tradition or operational convenience rather than natural history or population diversity are the norm for studies conducted within hospitals and their target populations. This makes translating study results to real world clinical scenarios difficult, further restricting applicability.
Fully decentralized trials using telemedicine, remote medication delivery and data capture have the ability to eliminate in-person contact between researchers and patients, significantly speeding up trial progress while decreasing costs. Industry players have widely welcomed such innovations facilitated by COVID-19 pandemic.
Potential cost savings associated with this approach are significant. According to one estimate, BE failure reduction could reduce expenditure by one quarter annually on bioequivalence studies; additional indirect savings might include faster product development by eliminating unnecessary failures; freed resources not used in bioequivalence studies can then be deployed on other projects). Increased productivity also brings the promise of lower R&D expenditures overall and could even address affordability concerns within advanced health-care systems; ultimately adaptive designs working hand in hand with regulatory innovation are crucial elements in driving drug innovation forward.
