Pediatric patients are not simply small adults. Children differ from adults in both disease pathophysiology and pharmacokinetics/pharmacodynamics (PK/PD). Yet historically, 80 percent of medicines used in children had little to no data guiding prescribers on proper use. In this blog post, I’ll discuss the challenges of developing drugs for children and explain how quantitative pharmacology […]Read More
The time is right to explore how sensor-enabled digital adherence monitoring systems can benefit patients, sponsors, and payers. Non-adherence to prescribed medications is a key issue facing our healthcare industry, costing the US healthcare economy between $100-300 billion annually, representing between 3-10% of total healthcare costs [1, 2]. Further, non-adherence also decreases our ability to […]Read More
I recently had the pleasure of attending a 1.5 day Certara forum for management on the applications of physiologically-based pharmacokinetic (PBPK) modeling and simulation in Chicago, IL. Our CSO Dr. Amin Rostami and Certara consulting scientist, Dr. Alice Ke aptly led the forum. The highlight of the meeting was discussing the latest challenges and trends […]Read More
Most clinical study participants want to know the results of trials they participated in. However, few are actually informed. Lack of communication and transparency jeopardizes the success of the clinical research enterprise. In this blog post, I’ll discuss a new model for communicating trial results in lay language with minimum added burden on sponsors and […]Read More
The notion that volunteers could be harmed in a clinical trial is every drug developer’s worst nightmare. Earlier this year, the drug company, Bial, investigated inhibitors of the enzyme fatty acid amide hydrolase (FAAH) in clinical trials as a treatment for pain. Tragically, one person in the volunteer group died, and six patients were hospitalized. […]Read More
In his most recent New York Times Magazine piece, “The Improvisational Oncologist,” Dr. Siddhartha Mukherjee, author of The Emperor of All Maladies: A Biography of Cancer, wrote, “In an era of rapidly proliferating, precisely targeted treatments, every cancer case has to be played by ear.”Read More
If you have ever argued, as we have, for the resources and time needed for model-based drug development (MBDD), you have likely encountered that irritating accountant in the room who says, “Sure, this modeling stuff sounds interesting, but how much MONEY will this save us?” My answer: $97M of savings per New Drug Application (NDA). […]Read More
Officially, Prof. Malcolm Rowland has retired. This scientific pioneer has been helping lay the foundation of a mechanistic understanding of pharmacokinetics since the 1960s. So you might think that he’d be ready for quieter pursuits. But this professor emeritus at the University of Manchester has no plans to stop actively teaching and guiding the pharmaceutical industry’s use of modeling and simulation. Here, we pick Prof. Rowland’s brain about the impact of pharmacometrics on drug development, the direction he sees the field going, and the secrets to his success as a scientist and teacher.Read More
In my work with biopharmaceutical companies, universities, and regulatory agencies, I fly a lot. Looking out the airplane window, the revolutionary impact of biosimulation on drug development struck me. Unfamiliar with the concept of biosimulation, or modeling and simulation (M&S)? You can think of it as the vast improvements in air travel that have been made in the last half century.
Modeling and simulation gets information about how something behaves without testing it in real life. For instance, say we want to design a plane that has maximum speed. But, we weren’t sure what type of wings would improve non-friction. We would use a computer simulation of the plane to estimate the effect of different wing shapes on the coefficient of friction under different conditions. The simulation would provide insights about decisions we could make for the plane without building one. That’s what modeling and simulation is.
Imagine this applied to the world of drug development. Biosimulation is transforming our approach to precision medicine and supporting critical decision making.Read More
Pharmacometrics uses mathematical models of biology, pharmacology, disease, and physiology to describe and quantify interactions between drugs and patients, including beneficial effects and adverse effects. I recently had the pleasure of talking to a thought leader, Dr. Lawrence Lesko, about the history of pharmacometrics and how it will continue to shape drug development in the future.
Dr. Lesko was Director of the Office of Clinical Pharmacology in the Center for Drug Evaluation and Research (CDER) at the Food and Drug Administration (FDA) for 16 years until his retirement in July 2011. He currently serves as Clinical Professor and Director of the Center for Pharmacometrics and Systems Pharmacology in the University of Florida, College of Pharmacy at Lake Nona in Orlando, FL.Read More
Ever noticed how people from different ethnic backgrounds respond differently to drugs? For example, you may enjoy having a few drinks with friends on the weekend. When your friends with Eastern Asian heritage drink alcohol, it’s not uncommon for their faces to turn red. This happens because many East Asians possess an enzyme deficiency for aldehyde dehydrogenase 2 (ALDH2). Alcohol is metabolized to acetaldehyde which is further broken down into acetate by ALDH2. When people with the inactive ALDH2 variant drink alcohol, acetaldehyde accumulates in their body causing facial flushing, nausea, and a rapid heartbeat.
Ethnic diversity in drug response and its impact on dosing has been well described for some drugs.1 A recent study of the most widely prescribed proprietary drugs in the US showed that, in around half of all cases, the recommended doses in Japan were considerably lower than both the US and European doses.2 Investigating the potential impact of ethnicity on pharmacokinetics often involves repeating clinical studies in different populations, which may be unnecessary in some cases. Physiologically-based pharmacokinetic (PBPK) modeling and simulation in virtual populations can uncover changes in drug disposition due to ethnic differences, providing supporting information for regulatory review and helping identify and optimize essential bridging studies.Read More
Making the right choices in drug development often means the difference between getting a new medication to patients and it ending up in the scrap heap of failed programs. There is a surfeit of publically available information on approved drugs as well as those currently in development. How can sponsors turn clinical trial data into […]Read More
Last month, Certara sponsored the 11th Pediatric Clinical Trials conference in Philadelphia. First, I have to say that the content of this conference was among the best I have ever heard. Each speaker added to the dialogue, and the group was able to share and collaborate on how to make meaningful improvements to the field of pediatric drug approvals.
The subject is complex, often heartbreaking, and in many ways can be defined as a “Catch 22.” It is extremely challenging (both logistically and ethically) to enroll children in clinical trials, yet without a proper and approved clinical process, physicians are left with inaccurate dosing and therapeutic approaches for children. The result is a continuation of the off-label, experiential ‘wild wild west’ of prescribing. Here’s some interesting factoids that were revealed at the conference:Read More
Last month, I was fortunate to be able to represent Certara® at the BIO International Conference in Philadelphia, PA. One of the most exciting sessions that I attended was the Personalized Medicine Plenary with Dr. Francis Collins, the director of the NIH. He discussed how the Precision Medicine Initiative (PMI) will revolutionize the approach to improving health and treating disease. In this blog post, I’ll discuss the goals of PMI and how this initiative aligns with our mission to use biosimulation and strategic regulatory writing to bring safer and more effective medications to patients.Read More
As a clinician scientist, I get really excited about helping sponsors develop new treatments for patients. For some diseases, the lack of a validated prognostic biomarker is an impediment to developing effective treatments. In this blog post, I’ll discuss how we worked with the Critical Path Institute (C-Path) Polycystic Kidney Disease Outcomes Consortium to gain FDA support for a prognostic biomarker for a rare disease, autosomal dominant polycystic kidney disease (ADPKD). Having a validated biomarker will help spur new research and clinical trials to find a treatment for ADPKD.Read More
What would you guess is the world’s most neglected disease? I bet that you wouldn’t pick tuberculosis (TB)— a disease that causes an estimated 9 million new cases and 1.3 million deaths annually. This infectious disease is caused by the bacterium Mycobacterium tuberculosis. TB usually attacks the lungs, but can attack any part of the body.
Patients infected with TB are typically treated with a standard six-month course of multiple antimicrobial drugs. It is quite difficult to get patients to adhere to this long course of treatment. Often, patients will fail to complete the entire drug course. This increases the likelihood of relapse and antibiotic resistance developing. Thus, there is an urgent need for shorter treatment regimens that minimize the risk of relapse. In this blog post, I’ll discuss how meta-regression modeling of relapse can inform TB clinical trial design.Read More
Dose normalization is a common calculation performed with pharmacokinetic parameters. The general process is to divide the PK parameters by the administered dose. This is performed for each individual or treatment group in a study, and then comparisons of dose-normalized parameters can be performed. But, why would we want to dose normalize PK parameters? What […]Read More
One of the most common questions posed by clinical operations experts when including pharmacokinetic sampling in a clinical trial is the following: “What is the time window we should allow for each blood sample?” My answer is always the same: “Don’t include any window.” I am almost always met with a confused look. The confusion is […]Read More
Mass balance studies are also called “C-14 studies” or “Absorption, Metabolism, and Excretion (AME) studies”. It is important to understand what you are trying to learn from the experiment. The primary objectives of a mass balance study are generally: To determine the mass balance of drug-related material following dose administration To determine the ratio of […]Read More
After a much longer delay that I expected, I am back to blogging on a regular basis. Today I want to discuss a common topic among clinical pharmacologists. How do you properly design a drug-drug interaction study? Defining Drug-Drug Interactions While these studies may appear complicated, they can be simplified very quickly to make the […]Read More