The drug is Cylert, which is otherwise referred to as Pemoline. The drug, which had been developed by Abbott Laboratories, was a central nervous system stimulant used in the treatment of attention-deficit/hyperactivity disorder (ADHD/ADD) (Willy, Manda, Shatin, Drinkard, & Graham, 2002). The drug was in the market for 30 years before it was recalled by the Food and Drug Administration (FDA) attributed to its side effects resulting in live toxicity. Abbott Laboratories was involved in the manufacturing of the drug from 1975 until its recall in October 2010. In 1999, the FDA had added a boxed warning on the drug highlighting that continued use of Cylert was likely to have potentially damaging effects on a patient's liver (Shader, 2017). The warning was intended to limit the prescription of the drug with the view being that doctors would understand the risks that the drug may bring about for their patients. However, Abbott Laboratories maintained its distribution of the drug irrespective of the warning leading to the decision to recall the drug from the market.
Cylert is an oxazolidine compound, which is chemically defined as 2-amino-5-phenyl-2-oxazoline-4-one taking the structural formula shown in the figure below. The structural formula played a key role in build on its effectiveness as a drug that affected the central nervous system. On one hand, the drug was supplied in the form of tablets that contained 18.75 mg, 37.5 mg or 75 mg of pemoline, which were administered orally (Willy, Manda, Shatin, Drinkard, & Graham, 2002). On the other hand, Cylert was also distributed in the form of a chewable tablet, which contained 37.5 mg of pemoline. Cylert also contained a wide array of inactive ingredients including corn starch, lactose, polyethylene glycol, and magnesium hydroxide among others. From the original trials conducted, Cylert was considered as having minimal sympathomimetic effects. However, these effects were later discovered in multiple studies conducted based on the high risk of liver damages for patients using Cylert. When developing a drug, pharmaceutical companies are expected to consider several key ethical implications, which would help determine whether the drug is as effective as may be anticipated. The first ethical implication is that the companies must ensure that the benefits of using the drug far outweigh the harm or side effects. Although a drug may be viewed as being effective in the treatment of a given health condition, the focus is on its side effects to determine whether it can be sold in the market. In the case of Cylert, Abbott Laboratories had developed a drug with the capacity to aid in the effective treatment of ADHD/ADD. However, the drug’s side effects far outweighed the benefits considering that patients using the drug experienced immense damages to their liver (Patriarca, Van Auken, & Kebschull, 2018). Therefore, this meant that continued sale of the drug was unethical, as it exposed the larger population to harm.
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The second ethical implication considered as part of the drug development process is the design and conduct of the trial. It is generally recognized that trials conducted during drug development ought to be sound and acceptable, which would mean that the results gathered from the study achieve the intended outcomes. In cases where the study is designed unacceptably, the outcome is that it may affect the validity and reliability of study outcomes; thus, affecting the effectiveness of the study. The third ethical implication is on the inclusion criteria and selection of participants for the human trial. For the results of the drug development process to be considered as being ethical, it is expected that all individuals will be given an equal chance of inclusion as part of the study. The selection approach utilized must give equal opportunity for all as a way of ensuring that the results remain valid and reliable.
During drug development, several potential values and belief systems would have been addressed as a way of ensuring that the process remains ethical. The first system that must be addressed is the high degree of uncertainty that a drug will achieve the intended success levels. Uncertainty is a common value system in drug development considering that the researchers involved in the process are not sure of the drug's success in the treatment of a specific condition. Researchers find themselves where it becomes much more challenging for them to deal with uncertainty arising from the new drugs that they develop. However, this highlights the importance of addressing the high degree of uncertainty with the view being that this would help eliminate doubt on the possibility of failure. Addressing this value system would ensure that the drug development process remains ethical; thus, guaranteeing the overall effectiveness of the ultimate drug developed. The second system that ought to be addressed during the drug development process is the safety of the drug. Safety remains as one of the key areas of concern when developing new drugs considering that some of the drugs are much more likely to harm users as opposed to improving their health. Therefore, this highlights the importance of addressing this system considering that it will help increase confidence in the drug developed. Additionally, addressing any safety issues may also help build credibility for the company involved in the drug development process. Lastly, efficacy is another system that must be addressed during drug development. Efficacy focuses more on defining the effectiveness of a drug while considering the value that it brings out for its consumers. Researchers have a key role to provide a clear outline of effectiveness associated with a specific drug, which would be of value in identifying possible issues, such as side effects among others. Cylert was pulled from the market by the FDA in October 2010 after it had been sold for close to 30 years. The main reason the FDA opted to pull the drug from the market was that its side effects were immense compared to the projected benefits for individual patients. Mental health doctors across the United States recommended the drug attributed to its effectiveness in the treatment of ADHD/ADD (Kubiszyn & Mire, 2014). However, the drug had the potential of damaging a patient's liver. The FDA had observed how patients responded to the drug for a while before deciding to pull from the shelf to be towards protecting the patient. According to the FDA, Cylert resulted in acute hepatic failure among patients with some of the cases reported dating as far back as 1975. The demand for a drug with the ability to treat ADHD/ADD was high attributed to the number of persons suffering from the mental condition across the United States. Abbott Laboratories embarked on a drug development process that involved the determination of the active ingredients to be included as a way of advancing its efficacy. The company undertook each of the steps involved in drug development after which it received approval from the FDA to market the drug. From the onset, it was clear that the drug’s effectiveness was overshadowed by the fact that some of the patients exhibited associated with acute hepatic failure (Shader, 2017). Most of the cases reported to the FDA were linked directly to the drug, which was prescribed by a doctor within the United States. The FDA embarked on a process of determining how patients responded to the drug depending on the sympathomimetic effects reported. Since Abbott Laboratories began marketing the drug, Cylert, the FDA had received 13 reports of acute hepatic failure. Although the number of cases report was not high, the rate of reporting ranged between 4 and 17 times higher than the overall population in the United States. Statistically, this means that continued use of the drug exposes many more patients to notable risks of liver damage, which is a key side effect associated with the drug. Out of the 13 cases report, the FDA had taken noted of the fact that 11 of the cases reported had resulted in death or liver transplant (Kubiszyn & Mire, 2014). That served as a clear indication of the need to pull the drug from the market to minimize risks to patients. Before deciding to pull the drug from the market, the FDA conducted its review of its efficacy considering every aspect of the drug, which led to the decision that it indeed posed a significant risk to patients. The reason the drug may have been approved initially by the FDA was due to the falsification of results from the clinical trials conducted to hide the side effects associated with the drug. Abbott Laboratories could have decided to falsify results from the human trials as a way of gaining approval (Patriarca, Van Auken, & Kebschull, 2018). Another reason is that the side effect, acute hepatic failure, can equally be attributed to other risk factors such as excessive consumption of alcohol, viral hepatitis, and idiosyncratic reaction to medications, such as tetracycline and troglitazone. During the approval stage, it would have been hard to detect the side effect, as human participants may not have exhibited any onset symptoms of liver damage. It took so long for the drug to be taken off the market due to a lack of adequate data on its side effects. The FDA may have overlooked the cases reported for the entire period the drug was in the market, as they did not have clear data to link Cylert to the side effects noted.
Following the recalling of Cylert, the FDA has an important role in enforcing the decision to remove the drug from the market. This means that the FDA would adopt proactive strategies to ensure that the drug is not prescribed to patients across the United States. The FDA may need to work with doctors in multiple states to ensure that Cylert is not prescribed to patients with the view being that this exposes them to much more harm compared to the benefits that they are likely to get from its use. The FDA may need to organize training and development programs with mental health doctors in different states from where it would educate them on the negative health implications associated with continued use of Cylert on liver damage.
The FDA may also need to create advertisements warning consumers of Cylert while outlining the effects that this drug may have when consumed. Consumers, on the other hand, have a key responsibility to report to the FDA any doctors prescribing Cylert even though it has been taken off the market. Through proper education, consumers will be in a much better position to identify Cylert; thus, reporting to the FDA for necessary action to be taken. Monitoring needs to be undertaken to ensure that companies involved in clinical trials for new drugs do not falsify the results of their trials. The FDA may need to work with these companies during their clinical trials to ensure that they consider all ethical implications to avoid instances, where drugs developed, have far-reaching side effects. The FDA may also introduce stiff penalties for companies involved in the falsification of clinical trial results as a way of making it much more difficult for companies to engage in such actions.
References
Kubiszyn, T., & Mire, S. S. (2014). A review of recent FDA drug safety communications for pediatric psychotropics. Journal of Child and Family Studies , 23 (4), 716-727.
Patriarca, P. A., Van Auken, R. M., & Kebschull, S. A. (2018). Analysis of the Risks and Benefits of New Chemical Entities Approved by the US Food and Drug Administration (FDA) and Subsequently Withdrawn From the US Market. Therapeutic innovation & regulatory science , 52 (5), 649-655.
Shader, R. I. (2017). Risk Evaluation and Mitigation Strategies (REMS), Pemoline, and What Is a Signal?. Clinical therapeutics , 39 (4), 665-669.
Willy, M. E., Manda, B., Shatin, D., Drinkard, C. R., D. J. (2002). A study of compliance with FDA recommendations for Pemoline (Cylert®). Journal of the American Academy of Child & Adolescent Psychiatry , 41 (7), 785-790.
