Below is the text of the Keynote Address I gave at the graduation ceremony for Campbell University’s Department of Clinical Research at the Duke University Searle Conference Center in 2005. The content, in part, addresses moral obligations in an area of the healthcare industry, in this case pharmaceuticals, that could be useful to readers in future articles this author will write on healthcare reform. Additionally, it also discusses some of the process for getting new therapeutic agents to market that might be of interest to some.
CAMPBELL UNIVERSITY DEPT OF CLINICAL RESEARCH
DUKE UNIVERSITY SEARLE CONFERENCE CENTER
NOVEMBER 11, 2005
Dean Maddox, Assistant Dean Moore, Professor Jamerson, honored faculty and staff of Campbell University School of Pharmacy and Department of Clinical Research, and the graduating class, it is a privilege to speak before you today. I wish to compliment Campbell University for establishing a program that will provide individuals trained in clinical research to the pharmaceutical and biotechnology industries.
I have been very fortunate in my career to have acquired a diverse background in business and the research and development of therapeutic agents. I have held research positions in academia and industry, I have been an executive overseeing the clinical development of drug products for one of the largest pharmaceutical companies in the world, I have been a corporate officer in a publicly-held pharmaceutical company overseeing research, development and manufacturing of therapeutic agents, I have been founder and Chief Executive Officer of my own drug development services company, and I have been a consultant to the pharmaceutical and biotechnology industries. I have held contractual relations with up to 50 different companies and have been involved in the development of dozens of therapeutic agents spanning from first time in man through post-market development strategy. It is from the perspective I have gained in these varied experiences that I speak to you today.
To the graduating class, you are entering into a wonderful and rewarding career. You will be playing a role in making products available that will alleviate pain, suffering, improve the quality of life, and even save lives. Your work will touch lives in a very meaningful and positive way. From a very personal perspective, my wife, who is in the audience, was diagnosed with an acute leukemia this summer. She was treated by a very talented and compassionate staff of clinicians and health care professionals in the building just next door. In addition to the outstanding medical care she received, had it not been for the therapeutic agents provided by the pharmaceutical industry to treat and support cancer victims, my wife would not be with me at this time. You will be able to walk into pharmacies and take pride in seeing products that you have helped to make available to treat illness.
Therapeutic agents can positively impact patients and their families. Let’s consider the area of oncology for some examples. The introduction of the serotonin antagonists in the early 1990’s to prevent nausea and vomiting associated with cancer chemotherapy changed the nature of cancer wards where patients had previously been sedated prior to treatment. These agents also improved chances that patients would be able to better tolerate, and thus complete, the full course of treatment, optimizing their chances of survival. Colony stimulating factors have shortened the time of recovery between chemotherapy treatments thus reducing infection potential and allowing patients to initiate additional treatment sooner and attack their disease more aggressively. No greater example need be presented here than the positive impact of supportive therapy in children afflicted with cancer, not only for the children but for the parents as well who experience the emotionally difficult situation of seeing their child undergo the rigors of treatment. Again, from a very personal perspective, my wife and her son share a common bond – both now have been leukemia patients. My wife’s son is a pediatric leukemia survivor and she supported him through the multiple adverse effects of treatment in the days when little supportive therapy was available. Thanks to new therapeutic interventions, today presents a very different picture for patients of all ages being able to better tolerate and complete cancer chemotherapy.
Another benefit of drug development, if it is done properly and astutely, is that it can further our understanding of disease. A new therapeutic intervention can be viewed as a tool that opens new insight into the mechanism or behavior of a disease thus creating the opportunity for further advancement. If an agent provides differential effect, that effect may enhance our understanding of the disease process. So do not underestimate the degree to which your career in drug development can positively affect people’s lives and advance our understanding of disease.
It is important that you always keep in mind the uniqueness of the products you are helping to develop as you execute your work. A pharmaceutical product is not a luxury item. In the majority of cases where these products are provided, they are not products of choice – rather, they are products of necessity. The decision to use a pharmaceutical product involves trust and hope that the agent is safe and will provide benefit to those who suffer. This element of trust and hope is shared by the physician, the patient, the family and other loved ones of the patient who wish to see the suffering stopped or the life saved. The business of the pharmaceutical industry resides in a single event – the decision to use a therapeutic agent to treat a patient. It is imperative that this decision be based on sound information generated from carefully planned and executed studies. The execution of clinical research must be done diligently and thoroughly with keen observation and thoughtful analysis. When one considers what is at stake with these products, there can be no lesser standard.
Additionally, the information regarding the performance of drug products should not be based on innuendo drawn from inadequate trials for the purpose of enhancing off-label product sales. Pharmaceutical and biotechnology companies where investors are involved (public or private) are under great pressure to deliver financial return. The pressures of the competitive market place are significant with companies trying to protect and grow market share in head to head commercial combat with their competitors. Executives and employees often have a vested interest in how well a company does through stock option and bonus programs. These pressures and influences can create conflict, cloud judgment and lead to poor decision making. It is not uncommon for corporations to buy influence in off-label indications by financially supporting thought leader clinician-consultants to speak at seminars or educational events, or financially supporting small inadequately controlled trials that produce little meaningful evidence of drug benefit but place a recognized name on a publication (sometimes ghost written through a marketing agency) or the podium. “On the Take”, a recently published book authored by Dr. Jerome Kessler, former editor of the New England Journal of Medicine, discusses how medicine’s complicity with big business can endanger patient health.
The origins of pharmaceutical industry regulation date back to the administration of Abraham Lincoln. History has repeatedly shown the need for pharmaceutical industry regulation, but business pressures and lobbying efforts have proven to be formidable obstacles over the years. The decision to use a pharmaceutical agent must be based on reliable and complete information from carefully planned trials, and thoughtful and diligent work. And that is where you come into the picture for you are the individuals who will, in large part, be involved in the planning and execution of clinical research efforts that will generate information. The development of pharmaceutical agents is indeed a wonderful and rewarding career. But, make no mistake about it ladies and gentlemen of this graduating class, considering both the nature and intended use of these products and the trust and hope that people place in these products, there is a degree of moral and ethical obligation that you will have in the execution of your career that exceeds that of most any other profession you could enter into.
The term clinical research includes the word ‘Research’. My graduate advisor once told me that research was the easiest occupation that one could waste their time at. Unless the work is properly planned and executed, results can be misleading or misinterpreted. For those of us who have been trained in research, we can relate to the pain and frustration during our training of having to re-do work because of a lack of attention to planning and detail. In the laboratory a mistake is usually tolerated reasonably well. In the world of drug development, a mistake borne from inattention to detail or carelessness can, amongst many things, place patients at risk or cause delays in the introduction of an important new medication to an awaiting patient population.
I once published the opinion that the development of drug products is a research-oriented process. Individuals participating at all levels of product development should by nature be inquisitive, having a keen eye for observation. The drug development process relies on a developing body of information generated from individual experiments; each set of results provides the rationale for the next step. No one discipline drives drug development. Information from the three major components of drug development (Chemistry/Manufacturing/Controls, non-clinical pharmacology and toxicology, and human clinical trials) must be assessed and integrated into a composite picture regarding the agent throughout the development process. Each of these major areas provides information about the product that will guide decisions regarding such things as potential uses, dosage strength and schedule, and areas of safety to be evaluated.
There are three components to the research process: planning, execution (data acquisition), and analysis (interpretation). In planning clinical trials, it is important that all existing information be considered. As some brief examples, the chemistry of the compound can be an indicator as to whether it will be bioavailable for a specific indication; and, non-clinical toxicology findings must be carefully considered in constructing areas of safety assessment. Execution of a clinical study involves proper set-up and data acquisition. Data acquisition must be done with a keen sense of observation. Every case report form becomes a building block upon which a data base will be built and each building block must be complete and accurate. Missing or incomplete information can result in an inability to accurately assess benefit/risk. Data analysis and interpretation must be done carefully and thoughtfully. Whereas efficacy is more of a statistical concern, safety tends to be more patient-specific. An efficacy endpoint can be defined; safety, however, involves the unknown. For this reason, trials are generally required to stand on their own regarding efficacy, but data can be combined from studies of similar design to assess safety. A statistically non-significant finding in the area of safety should not be readily dismissed. A finding of just 2 or 3 patients with a specific event can be an indicator of a larger problem and these events require exploration – again supporting the need for high quality data acquisition.
Whereas a company can plan its presentation of data in a drug application over a period of years, PDUFA has imposed tight timeframes on FDA to assess the approvability of an application. It is not surprising that FDA conducts its own independent analyses of data to verify and explore sponsor findings. Assure that your New Drug Applications are based on well planned and carefully executed studies, thoughtfully analyzed data, and complete information. Do not let FDA be the one to teach you about your product; strive to make your application a guiding light for the agency and the medical community.
Clinical research is a wonderful career and its benefits are many. Be dedicated to your profession; perform your work carefully, diligently and with the highest standards of ethical and moral conduct. Never forget that you will be part of the fabric of a company; be a good thread in that fabric for every good thread produces a better fabric. Never lose site of the intended purpose of the product – to alleviate pain, suffering, improve the quality of life and even save lives. Never forget that the hopes and trust of the physician, the patient, and loved ones of the patient will be founded in your contribution. I wish you well in your career. Thank you, and good luck.
Arthur R. Kamm, Ph.D.