With the goal of harnessing the untapped potential of Iranian-Americans, and to build the capacity of the Iranian diaspora in effecting positive change in the U.S. and around the world, the Iranian Americans’ Contributions Project (IACP) has launched a series of interviews that explore the personal and professional backgrounds of prominent Iranian-Americans who have made seminal contributions to their fields of endeavor. We examine lives and journeys that have led to significant achievements in the worlds of science, technology, finance, medicine, law, the arts and numerous other endeavors. Our latest interviewee is Kazem Kazempour.
Dr. Kazem Kazempour has been the President and CEO of Amarex Clinical Research since 1998. In addition, he serves an adjunct professor of bio-statistics and epidemiology at George Washington University's School of Medicine and serves on the university's Regulatory Affairs Advisory Board. Amarex Clinical Research is a globally active clinical research organization, working with international pharmaceutical, biotechnology, medical device companies, and the National Institutes of Health (NIH).
Dr. Kazempour began his career as a mathematical statistician working at the Genetics Institute in 1975. He has worked in various therapeutic areas in multiple capacities, including as a presenter to the Food and Drug Administration, as an FDA reviewer, and as a sponsor representative in diverse areas including anti-infective, AIDS, cardiovascular diseases, vaccines, and wound healing. He has chaired, established, presented to, and participated in, several Data Safety Monitoring Boards for compounds within his area of expertise, and has authored and refereed publications and technical reports both in and for mathematical statistical journals as well as clinical literature.
His expertise has earned him multiple recognition awards from the FDA for his contributions to the drug approval process, particularly for his work on HIV and AIDS clinical trial designs and analyses. He has designed and presented to the FDA meetings and FDA advisory committees on more than 100 different clinical trials and medical devices ranging from Antiviral, HIV, and septic shock, to diabetics and wound healing.
Tell our readers where you grew up and walk us through your background. How did your family and surroundings influence you in your formative years?
I was born and raised in Ahwaz, a city in southern Iran. As I was the 5th of 11 children (plus 2 additional older boys who stayed with us), my family was considered fairly large. My father was a mechanic by trade, as were all of my mothers’ brothers. In those years (in 1960s and 70s) the wages of mechanics were low. So, given the sizes of my family and my father’s wages, our family’s income was considered below average.
In my family, it was customary for boys to complete only elementary school. Thereafter, boys were to quit school and begin learning a trade such as electrician or mechanic. Given that my father and my uncles were all mechanics that is the trade I chose. At the age of 11 or 12 I quit school and, as a child, started as a mechanic's apprenticeship in my father's and uncles' auto shop.
It was in my uncle's business partner, Abdol Vahab Nakhoda Zadeh, where I found true rapport and mentorship. Mr. Nakhoda, as I called him, was a well-educated man. To me, he seemed the most educated, the most well-read, and the most socially- and politically-active person I had ever known. We became well-acquainted during the first few months of my apprenticeship. He told me that I quickly learned the work of a mechanic, and noticed how bored I became after I had mastered each new task he gave me. At every spare moment I was at the library or in some other quiet corner with my nose in a book or reading available newspapers to learn about events occurring in my country and around the world – mostly relying on his daily newspapers or books. My enthusiasm for events and literature delighted him. He often commented that continuing as a mechanic would be a waste of my time. He believed that I should be in school where I could learn more. He believed that education was a great key to success for those with a passion for learning. He believed that I had the needed passion and constantly aimed to gain my father's permission to be allowed to return to school.
After two years of goading and the offer of adopting me, my father finally relented. But, upon application for re-enrollment in school, we learned that my absence of two years prohibited my re-entry into the local high school, and “adult school” or “night school” were the only option. Being the socially- and politically-connected individual that he was, Mr. Nakhoda (my first real mentor) found a way to bypass this re-enrollment rule. And, at the age of 14, I re-entered the school system at the high school level. My formal schooling continued through high school, college, and a Masters Degree, and culminated in receiving a doctorate in statistics from the Colorado State University; however, I know well that education should never stop.
Throughout my formal education as well as in my day-to-day lessons of life, I have learned that knowledge is a gift worthy of life-long pursuit. It provides a key for the release from poverty, for the path to success, for a feeling of self-worth, and for the ability to help others. I have also learned that a good mentor is the lubricant which makes that key turn more easily. Together the key and the lubricant make it possible to unlock the “road to success” for those who have the courage and passion to do so.
You have received multiple recognition awards from the U S Food and Drug Administration for your contributions in the drug approval process. What are your most significant accomplishments that led to this recognition?
All of the recognition awards from the US Food and Drug Administration (FDA) were related to my work and contributions to HIV and AIDS drug development and approval during my FDA tenure as statistical reviewer for the Center for Drug Evaluation and Research (CDER). This division of the FDA is responsible for assuring that HIV drugs are safe and effective for use by people in the U S.
My tenure with the FDA began after several years with various US universities where I taught statistics, and employment with several US pharmaceutical companies. Most importantly, my work commenced at the beginning of the HIV epidemic when drugs for HIV and AIDS were first being developed; i.e., in the late 1980’s. These drugs included AZT, ddI and ddC which were the first drugs developed. In fact, throughout my FDA tenure, I was heavily involved in the review and the assessment of the safety and efficacy for these early and for subsequent HIV/AIDS drugs.
Then, as now, human clinical trial(s) incorporating a primary endpoint to judge the effectiveness of a drug were required for FDA approval. Given that HIV and AIDS were unknown disease entities and the mechanism of the disease in humans was unknown at the time, the only endpoint or “proof” that a drug was effective against the disease was the prolongation of life. It was obvious to many involved in the drug approval process that it required too much time and was too expensive given the urgent need for effective and safe medications to stem the spread and prevent the needless deaths that were occurring at a phenomenal and exponential rate. It was, therefore, imperative that a substitute or “surrogate endpoint,” to be discovered. I was heavily involved in the FDA acceptance of surrogate marker to be used as an alternative to the “endpoint of death” in clinical trials.
This quest involved the evaluation of a myriad of biological lab and clinical results that were being submitted to the FDA via the drug approval process. My position as statistical reviewer for these drugs allowed me access to extensive data. The challenge was to prove statistically that there existed either a biological or clinical objective measurement that correlated (or responded) in the same fashion as the endpoint of death. After many hours and days/nights we managed to establish correlation of CD4 cell with mortality of HIV/AIDS patients as an acceptable regulatory endpoint.
Through my discussions with, presentations to and the help of many FDA directors and other researchers, the concept of using CD4 came to count as a “surrogate endpoint” and was accepted for HIV/AIDS drug trials by the FDA. In fact, in December of 1994, my colleagues and I were asked to organize an international meeting to discuss designing AIDS clinical trials, at which I was able to present my data. To this day the CD4 cell count is accepted worldwide as the primary endpoint in evaluating new HIV/AIDS drugs.
What are the most significant research projects that you have undertaken at Amarex Clinical Research so far? What research avenues are you exploring for the next few years?
Amarex Clinical Research (Amarex) is a contract research organization that I co-founded in 1998 with a colleague, Ms. Sally Breisch. Amarex is an international organization with branches in Taiwan and in the Europe; we have approximately 100 employees, and work on a wide range of clinical products in an effort to obtain US Food and Drug administration (FDA) and/or EU regulatory agency approval, thereby helping to bring clinical products to market. We design, conduct and manage clinical trials all over the world. Our current clients include pharmaceutical, biotech, and botanical, and medical device companies from the US, EU, Australia, Taiwan, Korea, China, and Malaysia. The contracts include evaluating the potential of the clinical products, designing, collecting clinical data, analyzing and presenting the results and the information to regulatory agencies for approval of the clinical products.
By training, I am a statistician. I have taught biostatistics, statistics, and epidemiology at universities in the US and also in Iran. I am currently teaching biostatistics and epidemiology at George Washington University in Washington, D.C. Because of the heavy emphasis on statistics and its importance in clinical trials, we chose a name for the company that is derived from the Persian word for statistics: “AMAR.” We began the company using the name AMARx which combines the concept of statistics and pharmaceuticals, i.e., Rx. Later we formalized the company with the current name Amarex which combines the concept of statistics with excellence.
All of our research and work have the goal of regulatory approval for new drugs, vaccines, diagnostics, and medical devices. We have worked on a wide range of products.
In your view, what is the biggest challenge with which you field is currently grappling?
As there is no one way to develop a clinical product, it is important to analyze each product based on its own merits and to think “outside the box” for the clinical products' development program in order to come up with the most efficient way to conduct trials and analyze the research data that are being produced. Each product’s program has its own challenges; however, some challenges that are common to all are time efficiency, reduction in the numbers of patients needed for the trial, and being honest with what the data tell us regarding the product.
At the moment we are dealing with the challenge of how a clinical trial design might be modified in an ongoing clinical trial (i.e., Adaptive Trial Design). Twenty years ago, this concept was a taboo, that is no one could think of modifying an ongoing clinical trial! Amarex, however, is pushing the boundaries and trying to find scientifically acceptable ways of modifying an ongoing trial’s design while maintaining confidence that instituting modifications in the ongoing trial provides reliable safety and data. The reason we have undertaken this task is to improve time efficiency, reduce time to market and use less patients data. By being able to modify an ongoing trial, it would be feasible to reduce the numbers of trials and patients required for product approval; thereby “bringing safe and efficacious clinical products to patients faster.” This is the Amarex mission statement, and it inscribed on our organization's mission statement and in Amarex’s literature.
As analyzing the data obtained from the testing of new drugs in clinical trials is the final stage of the drug approval process, results and analyses must be accurate, reliable, and scientifically defendable. By using all of the computational speed and data that are currently available (i.e., simulation, pooled data, etc.) to assess new methodologies, it is possible to gain approval with more time efficiency and with fewer patients.
Could you please share with our readers more of your insights and significant research findings?
If I had to pick only one significant contribution it would be related to HIV drug analyses that I mentioned; i.e., using a surrogate marker for the outcome of death in HIV trials. Another would be related to the use of “prognostic factors” for drug approval. My involvement in using prognostic factors (or “covariates” as they are called in the statistical field) began while I was working at a pharmaceutical company before my tenure with the FDA. Then, while I was employed by the FDA, I further pushed the concept of using covariate analyses in FDA by arranging multiple meetings within the FDA and outside of the FDA. The covariate analysis is a concept whereby as many prognostic factors as possible are included in the design of a clinical trial. The inclusion of prognostic factors in the trial design serves as a catalyst in reducing the number of patients required and obtaining results in a more expeditious manner.
These days, both concepts (surrogate markers and analysis of covariates) are almost routinely included in all clinical trials. Our next challenge is to make “Adaptive Trial Design” an industry standard.
What made you choose combining an academic career with industry work? Tell us about the biggest challenge you faced as an academic, how you overcame it, and what you’d do differently now? What do you most appreciate about academia? What has been the best part of your career so far?
There is a saying: “Once a teacher, always a teacher.” It has proven true for me as I have been teaching throughout my entire adult life; first in Iran, here in the US as university professor, while working at pharmaceutical companies and the FDA, and also in my work at Amarex.
After receiving my PhD in statistics I became a faculty member within the department of statistics at the University of Central Florida. I worked in this capacity until I received my US work permit (i.e., Green Card). After university I went to work within the pharmaceutical industry and subsequently to the FDA as a reviewing statistician. It is interesting that while I was working as a professor I was also consulting as a statistician on the industry side; and while I was working as a statistician within the pharmaceutical industry and at the FDA, I was also teaching by giving numerous seminars. Even currently this saying is true as I teach at GWU while working at Amarex.
According to your company, “Successful drug development is a collaborative effort between industry and FDA scientists.” Viewing the FDA as a development partner and maintaining industry objectives” is your company’s philosophy. Could you elaborate on this?
Yes, this is Amarex’s philosophy. It is based on my experience working within the pharmaceutical industry, my experience within the FDA, and my experience as a researcher in academia. While working within the pharmaceutical industry in the 1980’s I felt there was an air of adversity from industry towards the FDA. However, once employed by the FDA it was obvious to me that FDA staff were extremely hard working and were intent on helping pharmaceutical industry to bring safe and efficacious products to market by making better use of trial design and methodology. As a result of this obvious disparity, we at Amarex advise our clients to view the FDA as a partner by getting them involved in the development of the clinical product as early as possible and letting the FDA know about challenges that occur and asking for their advice on trial design, data collection and even data analysis. This is the fastest way to clinical product approval in the US. Our mission at Amarex is “to expedite patient access to safe and effective clinical products.” This mission goes hand-in-hand with the concept that “Successful drug development is a collaborative effort between industry and FDA scientists.”
What kind of challenges do your clients face over the course of a clinical development program or single trial?
Aside from the challenge of discovering a new molecule or finding a new purpose/use for an existing molecule, some common challenges in drug development are (1) to reduce the number of patients required in a clinical trial and (2) to select the most relevant clinical endpoint available for a given indication.
Solutions to these challenges can be divided into three categories:
· Regulatory Strategy: What is the best regulatory pathway for approval of the product? There are many different pathways from which industry may select.
· Patient Recruitment: Patient procurement for participation in a clinical trial is always challenging. It is important to brainstorm the potential sources of individuals that are afflicted and involve as many of those sources as possible into the trial.
· Analysis Methodology: The methodology for analyzing the clinical trial data must be specified during the early stages of trial conduct. Generally the analyses cannot be changed after data collection has finished. All methods of analysis must be well thought out and detailed. These elements will help to assure and confirm reliable results.
I wanted to ask about your thoughts on your Iranian-American identity. What does it mean to be an Iranian-American to you?
This is a difficult question. Additionally, our thoughts regarding this answer are becoming more and more important as being an Iranian is thought of, by many, as a liability. I believe that we should be proud of our heritage and we should be proud of what each of us offers to our adopted country. I can say that I am proud of both elements: my Iranian heritage and my contributions to the US in my area of expertise. It’s interesting that most of my life has been spent here in the US, not in Iran. I have adopted this country as my own and have been given so many opportunities here, as will my children. At the same time, I love Iran and have many great memories of Ahwaz. It was the place that provided me with opportunities, including a scholarship to come to the US and obtain my Ph.D. and the opportunity to go back to Iran to teach at the University. Truly, I see myself as an Iranian-American and I want to assure that my children are proud of both pillars of their heritage (Iranian and American) by learning their native language as well as English, maintaining our old customs as well as new ones, and traveling to Iran to visit with relatives as often as is possible. I dream of establishing an Amarex-like organization in Iran in order to help the pharmaceutical industry there develop new clinical products in a manner consistent with the Western world.