Introduction
This is a review and critique of the Wonder Drug Protocol based on its design, objectives, criteria for patient inclusion, study procedures, and safety and efficacy parameters.
Design
Before the beginning of any clinical study, the research team and the sponsor must ensure that several components of the study are in place (World Health Organization, 2002). The study must be accurate and efficient in terms of design. It is imperative to balance all aspects of the business and scientific validity of the trial.
The Wonder Drug Protocol used a randomized, double-blind, placebo-controlled, and a parallel group design (Spilker, 2000). The main objective of this study design is to evaluate the safety and efficacy of Wonder Drug in patients who have a mild to moderate severity condition of probable Alzheimer’s disease (AD).
The design aims to demonstrate similar primary and secondary efficacy measurements, which would be the same as those used in other cases of anti-dementia trials. A good clinical trial research design provides objectives of the study design. This protocol has a clear objective for the study. The objective acts or provides guidance on primary and secondary endpoints for assessment during the study.
The protocol provides the aim of the clinical trial research at a 5-center phase II. The process involves screening of AD patients followed by a random process of assigning either a placebo or Wonder Drug everyday for 40 weeks, which would consist of 30 doses. The design indicates that half the patient will take placebo and the other half will receive the Wonder Drug. It also shows that the study shall be performed in one, three, and six months after the baseline.
This is adequate information that can answer pertinent research questions. However, the protocol does not provide any schematic diagram of the study design. The protocol shows the study duration after the baseline and sequences of administering both the placebo and the Wonder Drug.
The study design shows the amount of dosage for AD patients, dosing regimen for patients, packaging of the Wonder Drug in 5 mg tablets, and labeling of the drug as scratch off labels for all experimental drugs. It also shows that the drug shall be administered orally. These are requirements in a clinical trial study design, and this protocol clearly captures them.
It also shows drug storage and accountability, as well as dispense of medication. The protocol insists that the placebo and experimental drug must be stored in a locked cabinet with restricted access. At the same time, the place must have favorable conditions in terms of light and temperatures. There is also drug accountability during shipment, which requires acknowledgment. This must cover per patient administration and visits before and after the drug return.
The Protocol provides follow-ups of adverse events. The study investigators shall follow up all patients who exhibit any adverse cases until the condition ends, becomes medically stable, or until when the patient can no longer be reached for follow-ups. The protocol also shows that all participants who stop the study because of adverse outcomes shall receive medical attention as provided for in the treatment of participants based on the outcome of the study. It will sufficiently document and report all cases for further evaluation.
A study design should also indicate when participants should discontinue participation in the trial. For instance, the Wonder Drug Protocol shows that a participant may discontinue the trial in cases of laboratory test abnormalities. In this case, the laboratory outcome may indicate abnormal ranges.
Such patients may only continue the study at the discretion of the investigator. Laboratory technicians must monitor outcomes and report to the site in case of adverse results outside the required ranges. The investigator must make decisions that involve the patient continued participation or further tests.
The study design also accounts for patient confidentiality. It will adhere to the Declaration of Helsinki and Institutional Review Board (IRB) guidelines. All stakeholders in the study affirm that they shall maintain patient confidentiality, patient’s rights and protect patients against any form of violation.
In this study, all patients shall have unique identification numbers and initials of their names for reference purposes. Data analyses shall use a blind technique to protect patients’ identity. In case of any review of participants’ details outside the informed consent, the Protocol recommends a written permission from the participant. The sponsor and the investigator have recognized serious consequences that concern overlooking of ethical responsibilities in clinical trial research.
The study design identifies possible risks and provides steps to mitigating such risks. It has safety, risk, and adverse event provisions. In these cases, outcomes may warrant termination and treatment of participants.
The protocol also recognizes that death may be an adverse outcome from the trial. Risks may also involve patients’ withdrawal of consents, noncompliance with the protocol, loss of a responsible caregiver to facilitate visits, and in cases where a sponsor terminates the project. The protocol does not provide methods of mitigating all these risks.
While clinical trial research may have some benefits to participants in terms of monetary compensation or treatment, this study design fails to account for availability or lacks of any benefits to study participants. Sponsors, investigators and other stakeholders should clearly indicate benefits associated with the study trial.
Objectives
A clinical trial research should have a detailed description of both primary and secondary objectives and purposes of the study. The protocol meets this criterion by providing both primary and secondary objectives of the study trial.
The primary objective of the clinical trial research is to assess the efficacy of the “Wonder drug in improving both the cognition and overall clinical functioning of patients with Alzheimer’s disease” (Darn Good Drug Company, n.d). Further, secondary objectives of the project are to “study the efficacy of Wonder drug in improving activities of daily living (ADL), and in reducing depressive and behavioral manifestations of Alzheimer’s disease patients” (Darn Good Drug Company, n.d).
However, this protocol does not discuss any issues that relate to the study feasibility. Moreover, there are no details about resources, skills, and experiences of key figures in the study. The protocol also does not indicate any pilot study information prior to this study.
Criteria for patient inclusion
A good clinical trial study must include participants’ inclusion and exclusion criteria. In most cases, women of childbearing or breastfeeding tend not to take part in several studies. Generally, pregnant women should not take part in clinical trial studies, unless there is a clear reason for including them.
Investigators tend to recruit people of different ethnic, racial, and socioeconomic backgrounds to ensure that study benefits are evenly distributed among participants. This study has several inclusion and exclusion criteria to meet unique requirements of the Wonder Drug and placebo.
The first mandatory inclusion criterion for participants in this study is the informed consent, which both the participant and caregiver must sign before taking part in the study. The study would include women and men aged 50 years and above, and women must be surgically sterile or have two years of post menopause. No pregnant or lactating woman shall take part in the study. There were also specific tests and evaluations, which study participants, had to meet.
On exclusion criteria, the study did not include participants with any other critical neurological disease apart from AD. Moreover, investigators excluded alcoholics, substance users, and people with cases of schizophrenia. These procedures were guided by laboratory test outcomes.
Clinical trial participants are mainly volunteers. The protocol fails to show whether participants were “forced, coerced, or enticed into participating by the desire to please one’s doctor, get excess money, or misleading promises of a cure of an illness” (Medpace Clinical Pharmacology, n.d). These are wrong practices in clinical trials, which do not define a research participant as a volunteer. Volunteers also have the responsibility of ensuring that they satisfy all research entry criteria.
This is the inclusion and exclusion criteria in clinical trials. It defines research terms and provides characteristics of people who should or should not take part in the clinical trial. The criteria could include age, weight, disease states, medication, sex, socio-economic background, and allergy among other factors. These selection criteria offer safety to participants and protect the sponsor and investigators against possible lawsuits.
It is imperative to note that different clinical trial studies have various inclusion and exclusion criteria for study participants.
Study procedures
The protocol has study procedures based on different visits during the trial. The initial stage involves a screening visit. The protocol only insists on participants who have passed both inclusion and exclusion criteria and have signed the consent form.
During this stage, potential participants take part in different tests, such physical, laboratory, x-ray, blood tests, hematology, and other relevant tests to meet the requirements of the Wonder Drug. Patients must also score required points on the Hamilton Depression Scale. Moreover, this process also accounts for all concomitant medications used within the last 30 days. At this stage, trial participants must also review all study data.
The second visit is the procedure for conducting baseline activities, which is scheduled 30 days after baseline screening. Investigators shall randomly give participants their placebo and Wonder Drug at the baseline visit for a period of four weeks on a daily basis (30 doses). Half of the patient would take placebo while the rest would receive the Wonder Drug. The process involves laboratory tests based on the study schedule and vital signs. Laboratory technicians would observe any changes during these days and record them.
The procedure also involves conducting a third visit 35 days after the baseline visit. Investigators must conform to the protocol requirements based on the dates of conducting procedures. The procedure would involve drug return and evaluation of compliance with the protocol. In addition, investigators would also take note of any adverse effects and abnormal variations.
Another procedure involves the fourth visit. This happens three months after the baseline visit or with a difference of 14 days earlier or later. This process involves evaluation of abnormal events, variations in concomitant therapy, and participants’ safety assessment.
Finally, the fifth visit occurs six months after the baseline visit with a difference of 14 days either earlier or later. The visit must follow the study schedule. It also involves safety evaluation, changes in concomitant therapy, and adverse outcomes. The investigator also notes any changes based on screening outcomes. This is the last visit of the study.
The protocol provides a clear study procedure, which other research can duplicate in similar studies. However, this protocol fails to account for follow up visits after the conclusion of the study. Such visits are necessary to encourage many people to participate in later studies.
Safety
The protocol accounts for safety of research participants by focusing on the vital signs, participant examination, laboratory tests, and other relevant examinations. Safety analysis would involve the comparison of outcomes with baseline values and any changes during the trial period.
The study pays specific attention to adverse events (clinically or laboratory) among participants during the study. Hence, any cases of abnormalities are safety concerns to investigators and the sponsor. Moreover, any cases of emerging adverse outcomes shall also be of special interest because these are the main reasons for several study procedures.
The investigator would decide whether patients with safety concerns should continue with the study. For evaluation purposes, there would be records for adverse outcome treatments, type of events, affected body systems, and severity. The protocol also notes that frequencies of treatment for adverse outcomes are necessary for the record.
The sponsor shall rely on Safety Monitoring Board (SMB) to conduct safety procedures. This is an independent body, which ensures that all participants in the trial are safe during the study.
On this note, one can conclude that the protocol meets safety standards required in a clinical trial study.
Efficacy
The protocol has both primary and secondary efficacy measurements for the study. The primary efficacy parameter is “Alzheimer’s Disease Assessment Scale-Cognitive Score (ADAS-COG) while the secondary efficacy parameter is Mini-Mental State Examination (MMSE)” (Darn Good Drug Company, n.d). It posits that both primary and secondary efficacy measurements would be the same as others used in other anti-dementia studies.
In primary efficacy evaluations, the researchers would apply a suitable method for a parallel group with a design that can support several centers. It would involve the normal intent-to-treat evaluation. The process would be random for all participants who were eligible for the study. The study shall also focus on endpoints assessment or last observation available in the case of a patient.
The study has a clear efficacy, including primary and secondary analyses with relevant means of conducting subsequent evaluations.
Conclusion
The Wonder Drug Protocol has a standard clinical trial research. It meets most of the criteria used in such studies. Hence, it is a reliable tool for clinical trial research. It has long inclusion and exclusion criteria to ensure that only eligible participants take part in the study.
This ensures safety of participants and reputation of the sponsor and other stakeholders. However, a long list of exclusion and inclusion criteria may present considerable challenges during participant recruitment. Besides, there are no indicated benefits for the study participants, which could discourage many potential participants. The protocol also fails to account for feasibility of the study, any available pilot test, qualifications, skills, and resources required to ensure that the project is successful.
References
Darn Good Drug Company. (n.d). Protocol. Toronto, Ontario: Darn Good Drug Company.
Medpace Clinical Pharmacology. (n.d). Study Participant Information: Participating in Medical Research with Medpace Clinical Pharmacology. Cincinnati, Ohio: Medpace CPU.
Spilker, B. (2000). Guide to Clinical Trials. Philadelphia: Raven Press Ltd.
World Health Organization. (2002). Handbook for good clinical research practice (GCP): Guidance for implementation. Geneva: WHO the Offi ce of Publications.