Most people expect that doctors are knowledgeable, trustworthy, and will provide an accurate diagnosis for any ailment. In an eight hour shift a general practitioner can see over thirty patients. Additionally, there are thousands, if not millions, of conditions any given patient may walk into a doctors office with, from swine flu, and diabetes, to less common conditions like schizophrenia and sickle cell anemia. In March 2010, the Unites States Food and Drug Administration (FDA) approved ten new drugs and published 4 new drug safety communications (FDA). Between meeting with drug representatives and seeing patients, it appears being a doctor can easily consume more than forty hours a week. Finding the time to research and interpret drug trials does not seem like an easy task despite the fact that the American public is expecting their doctor to have all the answers. Drug trial protocols, study interpretations, and communication of trial results are all falling far short when it comes to supplying unbiased, accurate and discernable information to the nations’ healthcare practitioners.
Evaluating the seven year period from 1998 to 2005 has provided great insight into issues in modern medicine. The number of serious side effects and deaths caused by FDA approved medicines has nearly tripled (Mandavilli). Consider Tissue Plasminogen Factor, tPA. Doctor Phil Brewer chose to treat a patient of his with tPA, as he showed signs of an acute stroke. He prescribed the drug as directed but was astonished to find his patient died, and it was directly from the effects of tPA (Lenzer). Tissue Plasminogen Factor was originally touted by the American Heart Association (AHA) to save lives, but not five years later the organization elected to withdraw its claim unable to provide evidence to support it (Lenzer). The AHA has made themselves a prominent resource referenced by the media and has provided public health information for more than twenty years. A significant number of educated Americans would regard the claims of the AHA with respect, and consider them to be a reliable source. Initial support of tPA followed by withdraw is a concerning piece of information when it comes from a relied upon community resource.
Next consider Avandia, a drug designed to treat type II diabetes. With a successful advertising campaign, Avandia was one of the best selling drugs in the world in 2006 (Harris). However, four years later members of the FDA are stating that the drug should be removed from the market (Harris). A drug that had 3.2 billion dollars in sales in 2006 is now deemed unsafe by multiple health care professionals. The drug is still on the market today as the heated debate continues. Steven Nissan, a cardiologist of the Cleveland Clinic, has published a study showing that Avandia can increase your risk of a heart attack by thirty to forty percent (Mandavelli). This statistic is large enough for many healthcare professionals to discontinue treatment with Avandia. Other sources, including Dr. Janet Woodcock of the FDA, agree the data is far to disparate at this time to come to a final conclusion on the drug (Harris). The organizations that exist, primarily the FDA, to approve drugs for public safety cannot come to a consensus on this drug with the data available to date. This leaves the nations healthcare practitioners in a precarious situation. One report supports its use while another yields extensive concern for its safety.
Avandia and tPA are only two of many drugs that have been linked to death and continue to be controversial within the healthcare field. Some over the counter medications that have been pulled from the shelves in more recent years include Hydroxycut and Cold-eeze nasal spray. The list goes on. If the FDA cannot agree on the safety of drugs available for public use, it becomes increasingly difficult for doctors to decide on the best form of treatment. If the doctors are able to find the time to research data on a new medication there is often no consistency in the results. It appears the fundamental issue lies within the effectiveness of the drug trials.
A randomized clinical trial is the most rigorous method used in drug development and study to determine the safety and effectiveness of a drug (Luce, et al.). Unfortunately in practice, the way drug trials are conducted leaves considerable room for improvement. The speed at which the trials occur, the source of the funding, participant size, and the analysis of the results are all critical areas that need attention. A study looking at trials between 1999 and 2002, as well as those between 2003 and 2006, showed an average increase in time of seventy percent from protocol approval to database entry (Luce, et al.). At this time there is no benchmark for randomized clinical trials. With such an increase in time to complete a trial one would hope the results would be more accurate and beneficial to the public, but professionals say they are only more complex, time consuming and inefficient than in years before (Luce, et al.).
Another area of concern is the source of the money that allows many drug trials to exist. When a large pharmaceutical company has developed a new drug and stands to earn millions, if not billions of dollars in profit, it is easy to understand they may view a trial’s results in the best possible light. If the trial for their drug proves safe and effective, they are much more likely to receive FDA approval for their drug. In many cases the big pharmaceutical companies provide the funding necessary for their drug to be tested. This money may influence the researchers if they see their results linked to the likelihood of further work and funding. Cary P. Gross, an associate professor of medicine at Yale, published an analysis showing that industry sponsored research was positive 87 percent of the time compared to only 65 percent of the time when the research was funded by sources outside private industry (Lenzer). It is far to easy for industry sponsored research to minimize the risks and exaggerate the benefits (Lenzer). As well, if a research trial is privately funded and the results are unfavorable there is no law mandating that the trials results to be published. They can simply choose to design a new trial and begin again. Erik Turner, a former employee of the FDA, recently published research demonstrating that “when studies of antidepressants were negative, they were reported as negative only eight percent of the time, but when studies were positive, they were reported as positive ninety seven percent of the time” (Lenzer).
Interpreting the results of a research trial is a complex issue. The factors that should be analyzed in a trial include, but are not limited to, primary or tertiary care setting, the method used to select the participants, methods employed to detect health outcomes, study duration, assessment of adverse events, and sample size (Gartlehner, et al.). Consider existing studies on statins, a cholesterol lowering drug. The concern with many statin studies is that they exclude participants who were originally part of the clinical trial but chose to drop out due to negative experiences with the drug (Lenzer). When the results are being analyzed this one fact can considerably alter interpretation. If the one reviewing the trial is not educated to factor this into his or her analysis the conclusion may be inaccurate. Healthcare specialists must also consider if a study has excluded critical segments of the population. For example, a study that excludes various ages, races, ethnicities, or comorbid conditions, would diminish the relevance of the trial to some clinical decisions pertaining to the excluded groups (Luce, et al.). If it is left to the healthcare clinicians, such as doctors, nurses, pharmacists and physicians assistants to both, find the studies and determine the validity of the research, they will have limited time to focus on the more critical task of seeing and treating patients. It is clear the analysis of randomized clinical trials is not a straightforward process when so many variables exist lending to the quality of the study.
The FDA has begun to recognize the failures of the drug approval process and they have begun to implement some initiatives for change. A new database exists where all clinical drug trials of every FDA approved drug must be registered (Marsa). It is not likely that all of the healthcare practitioners are utilizing this new resource as of yet, but this is one of many improvements. Additionally, more employees have been hired to work within the FDA, specifically to review drug trial results (Marsa). They now have the power to force companies to do further studies even after a drug is approved (Marsa). In 2009 the American Recovery and Reinvestment Act provided $1.1 billion dollars to support effectiveness research of randomized clinical trials (Luce, at al.). As well, the FDA has established a Clinical Trials Transformation Initiative, which is a partnership between the private and public sectors to act together to improve the quality and efficiency of clinical trials (Luce, et al.). The initiative has combined the efforts of those in academia, government, private industry, and patient advocates among others, to address key areas including study design principals, data quality, study start up, and adverse event reporting (Luce, et al.)
Margo A., a new college graduate and practicing pharmacist in Raleigh, North Carolina, agrees with many of the stated flaws of clinical drug trials within the United States today. At the same time she believes the nation has strong research centers and research specialists. She urges one not to discount the fact that medicines, including the controversial Avandia, have provided a quality of life for many that should not be forgotten despite the systems flaws (A. Margo). Even tPA has saved many lives. This fact should be considered when recalling the tragedy of Phil Brewer’s patient after treatment with tPA. The medical successes that have occurred because of new drugs reaching the market quickly should not be dismissed. Currently available medications are allowing people to live longer than ever before. According to data presented by the National Center for Health Statistics, from 1900 through 2005, life expectancy at birth increased from 46 to 75 years for men and from 48 to 80 years for women (Health United States 2008). This upward trend in life expectancy suggests that modern science is doing many things right.
This information is not intended to make one question every recommendation made by a general practitioner. Rather it attempts to inform the public that the current drug approval system has some areas of much needed attention. If possible, it is best to receive a second opinion from another healthcare professional before one proceeds with treatment. In all cases, if a person can deal with a health issue without drug treatment they are far better off. Even the most thorough drug trials are not able to determine all the possibilities of how an individual may react. Until the process for carrying out clinical trials is enhanced and a set of minimum requirements is in place it is important for one to do some minimal research. Before taking a prescription one should determine if the drug is currently under scrutiny, or if the drug is considered controversial for treatment. The available drug pool is constantly changing. Healthcare specialists who have the job of choosing the best treatment for a patient can only be as good as the information provided.
How Much Does Your Doctor Really Know?
A., Margo. Personal Interview. 17 March 2010.
FDA/Center for Drug Evaluation and Research. Food and Drug Administration. Web. 3 April 2010.
Gartlehner, Gerald, et al. “Criteria for Distinguishing Effectiveness From Efficacy: Trials in Systematic Reviews”. Agency for Healthcare Research and Quality 06-0046, April 2006: 1-19. Web. 26 March 2010.
Harris, Gardinder. “Research Ties Diabetes Drug to Heart Woes”. The New York Times. n.p., 19 February 2010. Web. 10 April 2010.
“Health, United States, 2008; With Special Feature on the Health of Young Adults”. National Center for Health Statistics. United States, Chartbook, 2008. Print.
Lenzer, Jeanne. “Wonder Drugs That Can Kill”. Discover. n.p., 20 June 2008. Web. 9 March 2010.
Luce, Bryan, et al. “Rethinking Randomized Clinical Trials for Comparative Effectiveness Research: The Need for Transformational Change”. Annals of Internal Medicine. American College of Physicians, 30 June 2009. Web. 28 March 2010.
Mandavilli, Apoorva. “Rx for the FDA”. Discover. n.p,, 12 December 2007. Web. 10 April 2010.
Marsa, Linda. “Drugmakers: Prepare for a Smackdown”. Discover. n.p, 20 June 2008. Web. 28 March 2010.