Phases of Clinical Trials

1.

The process of clinical trials divided into four different phases 

1. The first phase: In this phase, a group of 20 to 100 people selected for the trails. This phase determines the favorable dosage of a drug that does not cause any harm to the people.
2. Second phase: 100 to 300 participants are tested in this phase. Safety of the drug is further checked. In this phase the efficacy of a drug becomes apparent.
3. Third phase: 300 to 3000 people are selected for the trails. It provides FDA and pharmaceutical company with more understanding of the efficacy of the drug. Most of the drugs are failed to pass this stage.
4. Fourth phase: after the drug released in the market fourth phase is introduced to collect the vital data about any side effects of that drug (Orlando clinical research center, 2016).  Several thousands of volunteer with the disease are tested in this phase

2.

A)

• TGA is responsible to make sure that enough safe therapeutic goods are released for the public use in Australia.
• TGA regulates the supply of the medicine.
• TGA also regulates or manage the supply of IVDs (in vitro diagnostic medical device), blood and its components, derivatives of plasma, sterilants, and disinfectants (Ghosh, Skinner, & Ferguson, 2006).

 B)

1. Assessment: a pre-market assessment, monitoring, and enforcement of the medical standard of the drug after it released onto the market and providing a license to the Australian manufacturer. All the manufacturer need to be registered or listed. And if the found any problem associated with the drug, TGA has the right to shut down the production and use of the medicine.
2. Risk assessment: the approach of TGA to risk management includes identifying and assessing and examined the risk caused by a therapeutic drug, apply the necessary measure to treat the risk after a period of time

3.

3 (A)

Pharmacokinetics is basically studying about what the body does to the drug after its administration. The factors affecting absorption of the drug in the body are the route of administration and the solubility of the drug. Bioavailability of a drug depends on the route of drug administration, for example, intravenous drugs have 100 % bioavailability. Once the drug absorbed it distributed to the other parts of the body with the help of plasma proteins. After that the drug is metabolized in different organs like liver and kidneys. After metabolism it excreted from the body via different routes like sweat and lungs (Bullock & Manias, 2013).

3 (B)

Pharmacodynamics is studying about what the drug does to the body. The drugs have different effects on the body due to various factors like chemical reaction inside the cell (Galbraith, Bullock, & Manias, 2011). The effects of the drugs available at the particular site of action are determined by the binding of a drug to its receptor site. (Atkinson, Huang, lertora, & Markey, 2012).

4.

The first pass effect is explained as the quick uptake and the metabolism of the drug agent into the inactive compounds by liver just after the drug has been absorbed and before it released in blood circulation. First pass hepatic metabolism determines that what fraction or part of an oral drug will reach to the blood circulation. An oral drug loses some of its parts because the liver removes the substances via metabolism from the GI and prevents distribution to the other part of the body. The drug after swallowing absorbed in digestive system reaches to the hepatic portal system and carried portal veins before the drug reaches the liver (Finkel, Clark, & Cubeddu, 2009). IV or sublingual drugs do not undergo first pass effect and has 100 percent bioavailability.

Orally administered drugs possess low bioavailability (less than 100 %). The drug has the bioavailability of 20 % the doses of a drug needs to be administered 5 times orally with a high first-pass effect to see the effect of intravenous administration. Example of the drugs that exhibit first pass metabolism includes aspirin and lidocaine. The drugs with low bioavailability like lidocaine cannot be administered orally due to its metabolic toxicity (LabCE, 2018).

5.

 A)

The manufacturer of glyceryl trinitrate (GTN) 600-microgram designs the tablets in a way so that they can dissolve quickly beneath the tongue. The sublingual part of mouth has the high number of blood vessels that allow the drug to easily or rapidly absorb (Singh, Chitranshi, Singh, Arora, & Siddiqi, 2013). The medicine should be used sublingually to provide an instant relief from the pain in angina attack. GTN tablets should not be swallowed and placed under the tongue, as it does not work if swallowed (Department of Health Therapeutic Goods Administration, 2016).

1. B) 1. General education: the tablets and sprays of GTN provide an instant relief from the pain in chest. Therefore, the patient should carry the medicine all the time.
2. Emergency case: the pain must be decreased within few minutes after taking the medicine if it does not happen then the patient or their family should immediately call for the ambulance (Michael, 2017).

Responsibilities of Therapeutic Goods Administration

6.

1. The pharmacist plays an important role in distributing prescriptions medicine to the public, checking the dose of the drug, to make sure that medicine is correct
2. To cooperative or discuss with the doctors about the prescription
3. The pharmacist is one who supervises the preparation of the medicine
4. counseling the public about the side effects of the medicine
5. They also maintain the medication history and drug profile of a patient (World health organization, 2017).

1. A registered nurse is responsible to administer a medicine by identifying the right person by checking the patient’s written documents or by asking the patient to state their name.
2. a nurse ensures that the medication is given to the person at the right time and according to the prescription
3. A nurse also reports if any side effects occur by using a particular medicine.
4. The registered nurses also notice any allergies that cause problems to the drug therapy recommended by the doctor.
5. Collect the information related to the patients’ medical history and compare it with MAR (medical administration record) to find out if any incompatible drug combinations are there (Choo, Hutchinson, & Bucknall, 2010).

A doctor is the main health professional in any health care system and needs to deliver a safe and effective treatment to the patient. Some of the responsibilities of a doctor include

1. A doctor is responsible to prescribe a right medicine to the patient to achieve the health goals already set for the diseased person.
2. The doctor needs to provide information about the medicine to the patient and their families to safe and timely use of the medicine.
3. To prescribe the medicine by keeping some point in mind related to the 50 % bioavailability and necessary doses of a medicine (Hardling, 2014).

7.

Types of drug errors

1. Knowledge-based (wrong drugs): these types of errors caused by the lack of knowledge. For example, giving penicillin to a person without any knowledge regarding patient’s allergies. Communication issues with the senior staff and collecting the drug-dosing data contribute to the knowledge-based errors (Nichols, Copeland, Craib, Hopkins, & Bruce, 2008). These types of errors also called slips and can occur due to the slips in concentration or attention at the time of routine prescription and dispense. For example, if the diazepam bottle is picked from a pharmacy when the intention was to take diltiazem.
2. Wrong route: these types of errors can occur due to applying an inappropriate rule or misapplying the rule. For example, if the diclofenac medicine is injected it into the lateral part of the thigh instead of the buttock.
3. Wrong time: incorrect times of administration.
4. Wrong patient: when the drug is administered to the wrong patient without checking the identifiers such as by asking directly to the patient, identity band and patient record identifier on the medical chart.
5. Wrong doses: when the calculation has not been done correctly and high or fewer doses are provided to the patient (Tiziani, 2013).

8.

A) System approach

• System approach identifies the situation of the factor that may cause human errors
• It includes the implementation of system changes that can reduce the occurrence of errors or decrease their impact on the diseased person.
• This approach attempts to identify or block the human errors before they cause harm.
• The basic premise of the system approach is that the humans are fallible and the errors may occur, even in the top organisations. The countermeasures in this approach are based on an assumption that the human condition cannot be changed but the condition under which the person is working can be changed.

• This approach works on a philosophy that errors are caused due to the weakness of the human and some specific people are prone to errors than the others
• The person cantered approach focuses on the errors associated with the unsafe acts and procedural violation by the people such as nurse, physician, anaesthetists, surgeons, and pharmacists.
• This approach views the unsafe acts as these occurs due to forgetfulness, poor motivation, carelessness, negligence, inattention and recklessness. The followers of this approach treat the errors as the moral issues and assuming that bad things happen to the bad people.
• The errors can be reduced by identifying the variation in people and targeting and/or punishing them
• This is a blame-oriented model and suggests that blaming a particular person is more satisfying than blaming a whole institution (Garfield & Franklin, 2016).

B)

In the Swiss Cheese Model, the defenses and barriers stated as the best way to stop the errors from occurring in a system based model. Each barrier can be assumed as the slice of cheese. There would be no holes in an ideal world but in the real world, different defenses are lined up just like the slices of Swiss cheese. When the holes are lined up, the system failure or error takes place. Therefore, this model can help to understand the errors before its occurrence. Barriers and safeguards can be implemented in a healthcare system to help prevention of errors. It is important to focus on the causes and reason of the system failure not on who is responsible for the error (Moyen, Camiré, & Stelfox, 2008). 

C)

Active failure: these types of errors are committed by some people who are in direct contact with the diseased person. 

1. Slips: for example prescribing or entering a wrong dose inpatient drug chart
2. Mistakes: mistakes originate from the incorrect analysis. For example administration of penicillin to a person who is allergic to it
3. Example of the lapses error is when someone forgets to administer the prophylactic antibiotic (Mahajan, 2011).

Latent condition: Latent conditions are the issues intrinsic to the system. This model implies that the circumstances can create an event for active failure to occur

1. Administrative level decision
2. errors provoking conditions
3. long-lasting weaknesses (Nichols, Copeland, Craib, Hopkins, & Bruce, 2008)
4. Issues related to the storage of the drug also cause drug errors.

9.

Factors associated with prescription:

• Lack of knowledge about the prescribed drug, recommended doses and the details of the patient contributes to errors associated with the prescription. This also includes wrong doses of a drug for example if IV vincristine is prescribed for the intrathecal administration.
• The incorrect preparation of infusant solutions. For example, 20 mmol KCL (potassium chloride) is mixed with 500 ml of fluid rather than 1000 ml.
• When the drug is not administered
• Drug storage issues also contribute to the drug errors. Nearly all the drugs have clear indication that it should be kept in refrigerator or at room temperature and direct sunlight should be avoided, when these instructions ignored or not followed medication errors can be occurs. For example, the potassium chloride is kept in a cupboard near sodium chloride. 
• The factors such as System failure, illegible handwriting, an inaccurate record of the patient’s history, confusion with the drug name, use of decimal points inappropriately, use of abbreviations that may confuse. for example, AZT leads to confusion between the Zidovudine and Azathioprine, and the use of verbal orders instead of record orders (Brady, Malone, & Fleming, 2009)
• Other possible factors associated with prescription are noise, fatigue, and poor communication.

References

Atkinson, A. J., Huang, S., lertora, J. J. L., Markey, S. P. (2012). Principles of clinical pharmacology. (3^rd ed.). San Diego, USA: Academic Press.

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.

Bullock, S. & Manias, E. (2013). Fundamentals of pharmacology. (7^th ed.). Pearson: Australia.

Choo, J., Hutchinson, A., & Bucknall, T. (2010). Nurses’ role in medication safety. Journal of nursing management, 18(7), 853-861.

Department of Health Therapeutic Goods Administration (2016). Glyceryl trinitrate tablets (anginine and glycinate). Retrieved from: https://www.tga.gov.au/alert/glyceryl-trinitrate-tablets-anginine-and-lycinate- https://www.tga.gov.au/alert/glyceryl-trinitrate-tablets-anginine-and-lycinate-0

Finkel, R., Clark, M. A., Cubeddu, L. X. (2009). Pharmacology. (4^th ed.). New York: Lippincott Williams & Wilkins.

Galbraith, A., Bullock, S. & Manias, E. (2011). Fundamentals of pharmacology. (6^th ed.). Prentice Hall: Sydney.

Garfield, S., & Franklin, B. D. (2016). Understanding models of errors and how they apply in clinical practice. The Pharmaceutical Journal, 296 (7890).

Ghosh, D., Skinner, M., & Ferguson, L. R. (2006). The role of the Therapeutic Goods Administration and the Medicine and Medical Devices Safety Authority in evaluating complementary and alternative medicines in Australia and New Zealand. Toxicology, 221(1), 88-94.

Hardling, M. (2014). General prescribing guidance. Retrieved from: https://patient.info/doctor/general-prescribing-guidance

LabCE (2018). First, pass hepatic metabolism. Retrieved from: https://www.labce.com/spg1094059_first_pass_hepatic_metabolism.aspx

Mahajan, R. P. (2011). Medication errors. Retrieved from: https://www.esahq.org/~/media/ESA/Files/Refresher%20Courses/2011/Medication%20errors%20(2011).ashx

Michael, S. (2017). Glyceryl trinitrate. Retrieved from: https://patient.info/medicine/glyceryl-trinitrate-for-angina-gtn

Moyen, E., Camiré, E., & Stelfox, H. T. (2008). Clinical review: medication errors in critical care. Critical Care, 12(2), 208.

Nichols, P., Copeland, T. S., Craib, I. A., Hopkins, P., & Bruce, D. G. (2008). Learning from error: identifying contributory causes of medication errors in an Australian hospital. Medical Journal of Australia, 188(5), 276-279.

Orlando Clinical Research Center (2016). The four phases of clinical research. Retrieved from: https://ocrc.net/the-four-phases-of-clinical-research/

Singh, M., Chitranshi, N., Singh, A. P., Arora, V., & Siddiqi, A. W. (2013). An overview on fast disintegrating sublingual tablets. International Journal of Drug Delivery, 4(4), 407-417.

Tiziani, A. P. (2013). Harvard Nursing guide to drugs. (9^th ed.). Elsevier: Australia.

World health organization (2017). Role of the pharmacist in the healthcare system. Retrieved from: https://apps.who.int/medicinedocs/en/d/Jh2995e/1.6.2.html