Phases of Drug Studies

Phase I studies examine the safety of a drug or device. It involves healthy volunteers ranging from 20 to 100, who are rewarded for being involved in the research. The objective is to ascertain the effects of the drug or device on humans and can last for several months.

Phase II

This phase tests the drug or device efficacy. It includes multiple hundred patients and lasts for months to two years. The study is mostly randomized control trials comprising of experimental and control groups

Phase III

Involves randomized and blind testing of multiple hundreds to thousand patients and can take many years. Pharmaceutical companies can ask for FDA approval after the completion of phase III. It provides the company with an in-depth understanding of the efficacy of the drug.

Phase IV

Phase IV studies are undertaken after the approval for consumer purchase. Pharmaceutical companies at this phase are aimed at comparing the drug with the ones existing in the market. It involves thousands of participants (Pocock, 2013).

1. a)    The therapeutic goods administration (TGA) is under the Department of Health and is charged with the responsibility of safeguarding and improving the health of the Australians. TGA achieves this by regulating therapeutic goods in Australia, in addition to the manner in which they are produced, imported, exported and promoted so that they are fit for human use. The regulation covers medicines sold by the counter and prescribed by the doctor or clinician, blood products and surgical implants among others (TGA, n.d.).
2. b)    The TGA regulates medications for use through pre-market assessment and licensing. The pre-market assessment involves the evaluation of the risks of products against benefits. TGA utilizes clinical and scientific professionals to make sure that the advantages outweigh any risk. TGA also regulates products by providing licenses, and thus medicines have to be indicated as ‘registered’ or ‘listed.’ TGA is thus able to take action against any drug found to be dangerous (TGA, n.d.)

Pharmacokinetics is the study of the time taken for a drug to be absorbed, distributed, metabolized, and excreted. Pharmacokinetics is significant in improving efficacy and minimizing the toxicity of a patient’s drug therapy. Pharmacokinetics has enabled physicians to comprehend the association between drug concentrations and their pharmacologic feedbacks. The impact of a drug is associated with its site of action. Thus it’s significant to observe this concentration.

Pharmacodynamics is the association between drug concentration at the active site and the resultant impact, in addition to the time taken and the concentration of therapeutic and severe effects. The effect of a drug existing at the site of action is ascertained by the binding between a receptor and the drug. There exists an association between the drug concentration at the receptor site and the pharmacologic impact (Wang, Wang, & Balthasar, 2008).

Some orally administered drugs such as pentazocine and morphine are immediately absorbed from the intestines and transported first through the portal system to the liver, in which they are expansively metabolized. This process is referred to as the hepatic first pass effect. Initial metabolic processes can take place during the phase of absorption in the gut wall or liver before reaching the bloodstream. This leads to a reduction in the drug concentration before it arrives in the circulation. This implies that some portion of the drug is lost. Most of the oral drugs first pass through the liver and are then transported to the systemic circulation from the gastrointestinal tract.

Pharmacokinetics and Pharmacodynamics

Therefore, the liver can extract substances from the GI tract, thus preventing its dissemination to other parts of the body. First pass metabolism (the bioavailable fraction) determines the amount of oral dose that will end up in the circulation. Drugs that are 100% bioavailable such as intravenous drugs do not undergo the first pass effect. If drugs with the bioavailability of less than 20% are to be administered orally, then they will have to be delivered five times the dose that is administered intravenously in order to have the same impact (Wu, Kulkarni, Basu, Zhang, & Hu, 2011).

1. a)    Glyceryl Trinitrate (GTN) 600 microgram tablets must be administered sublingually and are designed so because the area of the mouth contains an extensive supply of blood vessels that permit the drug to be absorbed fast. Also, GTN undergoes high first-pass metabolism in the liver, thus if administered orally, the liver will extensively breakdown/detoxify the active drug molecule and therefore making it ineffective. Sublingual administration bypasses the portal circulation of the liver and enables GTN to have direct access to the site of action (Shakya, Madhav, Shakya, & Singh, 2011).
2. b)    The GTN tablet should be kept in its original container. Transferring the tablets from their original container may cause the active molecule to evaporate from the tablets. The lid should tightly be closed after taking the tablet from it, and it should not be opened for over eight weeks. The tablets must only be taken by being placed under the tongue (sublingually) and allow them to dissolve slowly (Shakya, Madhav, Shakya, & Singh, 2011).

1. a)    Registered nurse

A registered nurse has the role of reporting errors. Hoffmann, Beyer, Rohe, Gensichen, and Gerlach, (2008) observes that nurses have a function of disclosing any medication errors or hazards as a way of them improving in their practice and ensuring safe patient care environment. The nurses have the responsibility of incorporating pharmacodynamic and pharmacokinetic principles when administering medications to ensure patient safety.

They also have the role of recognizing perceptual factors to avoid mistakes made due to familiarity, similarity, and expectancy. Nurses have a responsibility of understanding the system and environmental factors to avoid any factors that may lead to medication errors. They also have the role of appreciating human factors such as inadequate communication and endeavor to address them (Durham, 2015).   

1. b)    Doctor

Conduct review and assessment of case reports for each handed in from clinical studies, random, and petitioned reports. Conduct triage of cases and ascertain severity and associations of all products as provided. Doctors also assess and confirm proper selection of extreme events from source documents, find out appropriate MedDRA code, assess labeling and review the narrative. Doctors also identify regulatory report potential of cases handed in from clinical studies, random and petitioned reports within specific therapeutic team. Doctors also play the role of attaining and maintaining existing knowledge of product selection and safety profiles for drugs in the entire therapeutic segment (James Lind Institute, 2016).

1. c)    Pharmacist

The American Pharmacists Association (2016) reports that pharmacists across the world have the primary responsibility of improving patient safety by ensuring that they receive appropriate medication. They ensure that access to medication by assessing the patient’s ability to pay for the correct medication and provide alternative medication options or means of payment. They also supply medication information by educating patients and care providers on the safety use of medication. Pharmacists also evaluate the appropriateness of medication. Additionally, pharmacists improve medication adherence by assisting patients to take medications based on prescriptions. They also assess the health status of the patients before and after medication.

Roles and Responsibilities of Healthcare Professionals

Knowledge-based errors. This is caused by lack of knowledge relevant to the given drug prescription. For instance, prescribing penicillin to a patient without first determining whether the patient is allergic or not, thus necessitating the importance of education (Aronson, 2009).

Rule-based errors- these are medication errors caused by misapplying an appropriate rule or using a bad rule. For example, administering diclofenac via injection on the thigh instead of on the buttock. They can be avoided by using computerized systems of prescription (Aronson, 2009).

Action-based errors. These are errors caused by lack of attention or distraction while carrying out medical procedures. For example, reaching out for diazepam bottle from the shelves instead of diltiazem which was initially intended.

Memory-based errors. These medication errors are caused by memory lapse or forgetting while knowing the right thing to do. For example, prescribing penicillin to an allergic patient due to forgetfulness. These errors are difficult to avoid and can be mitigated through cross-checking and by using a computerized system of prescription (Aronson, 2009).

Technical errors. These errors are caused by a technical miss-up such as the illegible writing of ‘panadol’ instead of ‘priadel’ (Aronson, 2009).

1. a)    The person-centered approach focuses on the risky activities, errors and procedural mistakes of individuals on the front line, i.e., nurses, surgeons, doctors, etc. The approach perceives the unsafe acts as majorly caused by deviant mental processes like inattention, negligence, forgetfulness, etc. the proponents of this approach perceive errors as moral issues and that bad things happen to bad people. These errors can be addressed by minimizing needles variability in human conduct. On the other hand, the system approach to human errors is based on the premise that humans are fallible and thus prone to errors, even in the best work settings.  Errors are perceived as consequences instead of causes. These comprise of recurrent error traps at the place of work and the organizational systems that cause them. According to Van Beuzekom, Boer, Akerboom, and Hudson (2010), these errors can be mitigated by making changes to the work conditions since the human condition of infallibility cannot be changed.
2. b)    Improved-technology systems have several layers of defense: some are engineered (spontaneous shutdowns, alarms), some depend on humans (doctors, anesthetists), whereas others rely on administrative protocols. They serve to protect potential victims and devices from native threats, but also have weaknesses. In a perfect environment, each layer of defense is intact, however, in real life situations, they are just like slices of Swiss cheese with several holes, although, contrary to the cheese, these holes always open and close, thus changing their position. The existence of holes in any of the slice is not an automatic indication of a bad outcome. Typically, this occurs when the holes in most of the layer happen to line up and thus allow a trajectory of accident opportunity, thus causing harm to patients. Thus, the defenses, safeguards, and barriers serve to ensure that the holes or errors do not momentarily line up and cause a medication error (Salmon, Lenné, Stanton, Jenkins, & Walker, 2010).
3. c)    Latent conditions

Poor organizational policies. For instance, an intricate surgical antibiotic prophylaxis protocol is likely to increase the incidences of incorrect doses in a single unit (Ghaleb, Barber, Franklin, & Wong, 2010). The second possible latent condition is equipment that is not designed correctly. An example is the lack of safety mechanisms to reset the rate of infusion pumps, leading to over-infusion of medications (Wilson et al., 1998). Protocols that are poorly written and the application of dose escalation trials can result in prescription errors (Parshuram, To, Seto, Trope, Koren, & Laupacis, 2008).

Active failures

Attentional slips are possible active failures that take place when the clinician fails to observe the progress of standard actions at some critical phase. Memory lapse occurs when an individual forgets the initially intended action like forgetting to inquire ones allergic condition before administering penicillin. Another example is rule-based errors such as the inappropriate application of existing procedures.  For example administering diclofenac via injection on the thigh instead of on the buttock (Aronson, 2009).

Distractions in the environment caused by carrying out tasks simultaneously such as undertaking drug round while at the same time supervising staff and responding to phone calls (Brady, Malone, & Fleming, 2009).  

Training and education. McMullan, Jones, and Lea (2010) found out that the modern approach of drug calculations in most of the nursing institutions did not factor in the clinical context and made was dependent on the ability of the students to manipulate numbers. Students’ poor in basic mathematical skills ended up with wrong drug calculations.

Causes of Medication Errors

Overworking. Studies had indicated that the risk of making medication errors substantially increased among registered nurses when they were engaged in work shifts of over 12 hours each week (Griffiths et al., 2014).

Understaffing and inadequate resources. Keers, Williams, Cooke, and Ashcroft (2013) found out that workplace conditions such as understaffing and scarce resources led to multiple medication errors

Wrong patient and wrong dose. Al-Shara (2011) conducted a study on the factors that influence to medication errors and found out that selecting the wrong patient or dose led to different medication errors. This was likely caused by Ineffective organizational protocols on treatment.

References

Al-Shara, M. (2011). Factors contributing to medication errors in Jordan: a nursing

perspective. Iranian journal of nursing and midwifery research, 16(2), 158.

American Pharmacists Association. (2016). Pharmacists’ Impact on Patient Safety: A Joint

Project of the American Pharmacists Association Academy of Pharmacy Practice and Management and Academy of Pharmaceutical Research and Science. Washington, DC. Retrieved from https://www.pharmacist.com/pharmacists-impact-patient-safety 

Aronson, J. K. (2009). Medication errors: what they are, how they happen, and how to avoid

them. QJM: An International Journal of Medicine, 102(8), 513-521.

Brady, A. M., Malone, A. M., & Fleming, S. (2009). A literature review of the individual and

systems factors that contribute to medication errors in nursing practice. Journal of nursing management, 17(6), 679-697.

Durham, B. (2015). The nurse’s role in medication safety. Nursing2018, 45(4), 1-4.

Ghaleb, M. A., Barber, N., Franklin, B. D., & Wong, I. C. K. (2010). The incidence and

nature of prescribing and medication administration errors in paediatric inpatients. Archives of disease in childhood, adc158485.

Griffiths, P., Dall’Ora, C., Simon, M., Ball, J., Lindqvist, R., Rafferty, A. M., … & Aiken, L.

1. (2014). Nurses’ shift length and overtime working in 12 European countries: the association with perceived quality of care and patient safety. Medical care, 52(11), 975.

Hoffmann, B., Beyer, M., Rohe, J., Gensichen, J., & Gerlach, F. M. (2008). “Every error

counts”: a web-based incident reporting and learning system for general practice. BMJ Quality & Safety, 17(4), 307-312.

James Lind Institute. (2016). Role of Physicians in Drug Safety. Retrieved from

https://www.jliedu.com/blog/role-of-physicians-in-drug-safety/ 

Keers, R. N., Williams, S. D., Cooke, J., & Ashcroft, D. M. (2013). Causes of medication

administration errors in hospitals: a systematic review of quantitative and qualitative evidence. Drug safety, 36(11), 1045-1067.

McMullan, M., Jones, R., & Lea, S. (2010). Patient safety: numerical skills and drug

calculation abilities of nursing students and registered nurses. Journal of advanced nursing, 66(4), 891-899.

Parshuram, C. S., To, T., Seto, W., Trope, A., Koren, G., & Laupacis, A. (2008). Systematic

evaluation of errors occurring during the preparation of intravenous medication. Canadian Medical Association Journal, 178(1), 42-48.

Pocock, S. J. (2013). Clinical trials: a practical approach. John Wiley & Sons.

Salmon, P. M., Lenné, M. G., Stanton, N. A., Jenkins, D. P., & Walker, G. H. (2010).

Managing error on the open road: The contribution of human error models and methods. Safety science, 48(10), 1225-1235.

Shakya, P., Madhav, N. S., Shakya, A. K., & Singh, K. (2011). Palatal mucosa as a route for

systemic drug delivery: A review. Journal of controlled release, 151(1), 2-9.

Therapeutic Goods Administration (TGA). (n.d.) How the TGA Regulates. Retrieved from

https://www.tga.gov.au/how-tga-regulates 

Van Beuzekom, M., Boer, F., Akerboom, S., & Hudson, P. (2010). Patient safety: latent risk

factors. British journal of anaesthesia, 105(1), 52-59.

Wang, W., Wang, E. Q., & Balthasar, J. P. (2008). Monoclonal antibody pharmacokinetics

and pharmacodynamics. Clinical Pharmacology & Therapeutics, 84(5), 548-558.

Wu, B., Kulkarni, K., Basu, S., Zhang, S., & Hu, M. (2011). First-pass metabolism via UDP-

glucuronosyltransferase: a barrier to oral bioavailability of phenolics. Journal of pharmaceutical sciences, 100(9), 3655-3681.