DRUG DEVELOPMENT-SIMBAREX 12
Acomprehensive project plan provides guidelines on how activities takeplace throughout the lifecycle of a project. This plan, inparticular, will act as a roadmap for the staff in the management,R&D, and operations departments in PureO2, in as far as theorganization of the activities that will be done on a daily basisthroughout the drug development processes of Simbarex.The details of the plan will be organized in multiple subtopics thatare deemed to be essential for consideration, starting off with theoverview section.
Overviewof the Plan
Theessence of drug development is to ensure that not only are novelmedicines identified, but there must also be the goal of ensuringthat they function to improve the overall quality of life ofpatients. It is critical to note that scientific advancements havefacilitated an in-depth understanding of disease processes, whichoccur at the molecular level (PhRMA, 2015). The need for using drugsto manipulate disease processes at the molecular level is the basisof Pharmaceutical Research & Development, of PureO2 per se.
Theprocess of drug development is considered to be lengthy, as pointedout by PhRMA (2015). The truthfulness of this information isexemplified by the fact that it might take close to a decade of theprocesses between drug discovery and marketing of a ‘newlydiscovered’ drug (PhRMA, 2015). In addition to the time factorconstraints, drug development is affected by cost constraint factors.In fact, as pointed out by PhRMA (2015), the cost incurred duringdrug development may be in the tune of billion dollars. The cost offailures mar the pharmaceutical research processes with figures ashigh as 80% failing to reach the screening phase, given that lessthan 12% of drugs that find themselves in the screening phase end upreceiving approval (PhRMA, 2015).
PureO2understands the risks that go into drug development as well as theplace of both time and cost in drug development. The company iscommitted to the investment of Simbarexdevelopment, bearing the implications arising from the aforementionedfactors. PureO2 is dedicated to ensuring that hope is restored to thecardiovascular health of patients, by dint of the development ofSimbarex.The drug will not only address the electrolyte balance that isimperative for the achievement of cardiovascular homeostasis but willalso limit high cholesterol levels that are present in the blood ofsome patients, thus, providing relief to patients and as a result,increase longevity to the years of the patients.
With the above in mind, a look at the operational steps that will beincorporated in the developmental phases will be identified. A GCPtraining regimen will also be mentioned in the plan, as well as theresponsibilities of individuals that are critical to Simbarexdevelopmental processes. The steps that would be taken in thecreation of both report forms and a database will be incorporatedinto the plan, without forgetting the details of audits that will beused during the drug development process.
Phasesof Drug Development
Adrug that is deemed as being the ideal candidate for possible usagein the clinical setting must go through rigorous processes thatfunction to ensure its safety, effectiveness, and efficacy, prior itsapproval by the FDA (PhRMA, 2015). The processes that are aimed atidentifying the above possibilities in a candidate drug are carriedin the form of clinical trials. The tests employ the use of patients,who are considered as being key players in drug discovery anddevelopment processes (PhRMA, 2015). PureO2 realizes that clinicaltrials are a major undertaking that requires significant planning,regulation, infrastructure, regulation and safety measures. On thatnote, the company will undertake clinical trials on Simbarex,which will be propelled in four phases dubbed I, II, III, and IV, asindicated below.
Inphase I, Simbarexwill be tried on a pool of people for the very first time. Thevolunteers in the trial will constitute of healthy individuals.
TheApproximate Number of Patients
Thenumber of people that will volunteer in the trial will be about onehundred.
PhaseI trial will be aimed determining the safety of the drug whenadministered to humans. In the bid to establish the safety level ofthe drug, information on pharmacokinetics and pharmacodynamics willbe determined
Theoperational steps in Phase I will take note of the followingprocedures: The first group of volunteers that partake in the study,considered as the cohort, will be given a small dose of Simbarex.The next group of the volunteers will be given an increased dose ofthe drug if the cohort group responds well to the first dose. Theresearch team will, therefore, monitor the impacts of the drug untilthe best dose is identified.
Inthe bid to establish the safety level of the drug, information onpharmacokinetics and pharmacodynamics come in handy. Under thepharmacokinetics property, information on absorption, metabolism, andelimination of the drug will be identified. Under pharmacodynamics,the possibility of side effects as a result of the usage of the drugwill be ascertained.
Havinggathered all the necessary information regarding the topics presentedabove, a safe dose that can be administered to humans can beidentified. Simbarex,if proven safe, a dosing regimen will be identified, and the trialwill then proceed to the Phase II.
PhaseII will incorporate volunteers who have cardiovascular diseases(hypertension and patients with high cholesterol levels).
Thepurpose of the clinical trial at this phase will be to ascertain theeffectiveness of Simbarexasa hypertensive drug.
TheApproximate Number of Patients
Thenumber of volunteer patients with the aforementioned cardiovasculardiseases will be in the range of between one hundred and fivehundred.
Theoperational steps that are critical to the study involveadministering the study drug as well as a totally different drug(either a dummy (placebo) or a drug that is currently available,which is used to combat the disease), to a randomized pool ofvolunteer patients. The trials in the clinical phase also involve theidentification of the optimum strength of the drug dose as well asthe dosing regimen that can be administered to the study patients.Additionally, examination of the adverse effects associated with thedrug use, as well as the risks that emanate from the usage of thedrug under study. If Simbarex showsexcellent potential, preparations for the third phase will ensue.
PhaseIII is critical in the identification of relevant statisticalinformation regarding the safety, risks, and effectiveness of thedrug under study.
Thepurpose of the clinical trials at this stage is to determine thesafety and efficacy of the drug under study. The trials in the thirdphase are also critical in the determination of the labeling and theinstructions that can be incorporated therein.
TheApproximate Number of Patients
PhaseIII trials of Simbarexwill involve a large pool of volunteer patients who will be drawnfrom multiple sites which are inclusive of hospitals. The approximatenumber of the patients will be in the tune of thousands, between1,000 and 5,000, or more.
Theoperations in Phase III involve the coordination of the sites andstatistical data retrieved therefrom. Coordination from the staff ina particular site, as well as IRB and FDA, will be done on the stagein the bid to monitor the trial adequately. A clinical researchorganization will work with PureO2 for recruitment and arrive at thedaily operations during the trial. The company will also work towardsacquiring the FDA approval before Simbarexthe can hit the market in phase IV.
Thetrials at this step will be done after the company has received theFDA approval and licensure of selling Simbarextothe U.S. market.Thestage is also considered to be a critical surveillance that happensafter marketing of the drug.
Thepurpose of conducting the trial in Phase IV is to garner moreinformation on the side effects that manifest with the usage of thedrug, risks and benefits (in the long run), and drug efficacy with abroad application. The drug effects are tested on specific groups ofpeople. The trials are also done to identify newer market segments(competitive analysis studies).
TheApproximate Number of Patients
Thenumber of patients that are considered in the stage is infinite(massive populations).
Theactivities undertaken in the phase will revolve around post-approvalresearch and monitoring.
Havingidentified the stages involved in carrying out clinical trials,understanding of the training that is required to be conducted onstaff regarding GCP in the trial sites is vital. Additionally, theroles played by certain stakeholders in clinical research i.e.monitor and study coordinator is necessary. The sections of the planbelow will address the information presented earlier.
Trainingprovided to the Sites regarding GCP Responsibilities
Thetraining that will be offered to the clinical trial sites regardingGCP responsibilities will incorporate the following: the trainingwill ensure that the staff members involved in the clinical trialsreceive education and awareness on matters revolving around trialdesign, audits, monitoring, analysis recording, conduction andreporting of clinical trials. The aforementioned activities will bedone in such a manner that assurance rests in the reported data in asfar as credibility, validity, quality and accuracy is concerned.Additionally, the reported data will ensure that the overall welfareof the clinical research subjects is emphasized and upheld.
Responsibilitiesof a Monitor with regards to Site Management
Monitorsplay a fundamental role in protecting the well-being of the researchsubjects in a clinical investigation (Welch, n.d). On that note, theresponsibilities of the monitor investigating PureO2 clinicalresearch on Simbarexinas far as maintenance of the welfare of the research subjects’safety is concerned will involve the following. Provide instructionsto the team members in the clinical research regarding therequirements of the protocol. The monitor will ensure that theinvestigators are aware of their responsibilities. Also, the monitorwill function in the verification of the adequacy of the sitefacility as well as the regulatory documents. The monitor will alsocheck to confirm that the drug under study (Simbarex)is on site, as well as other supplies. Finally, the monitor will makea review of the expectations and schedule used during the monitoringexercise.
StudyCoordinator Responsibilities to the Patient Population
Astudy coordinator functions as the link between the management and agiven clinical research under the care of a particular investigator,by playing coordinating duties (IRB Policy, 2013). The roles of an SCin PureO2 regarding the patient population involves the following.Facilitating the exchange of information between the researchsubjects (patients) and other stakeholders. The coordinator will alsoconduct screenings to select the patients who will be involved in theclinical research study. The SC will also offer an evaluation of thepatients` clinical examinations. The SC will be in a position to takevital signs that the patients would portray. Finally, the SC willalso have the ability to take samples/ specimens from the researchsubjects.
Data management is a vital component in pharmaceutical studies inproving or disproving the safety and efficacy that is associated witha particular drug (Meredith, n.d). It is a process of reviewingcollected data as mentioned by Meredith (n.d). In the pursuit toenhance data management, the development of case report forms, aswell as a database is necessary. The section will address the stepsthat go into the development of case report forms and a database.
CreatingCase Report Forms
CRFwill be designed to collect data described by a protocol.Documentation will be done regarding the design of CRF, development,approvals as well as the control of the versions. The CRF will beaccessible to the clinical locations before specific subjectenrollment. Training documentation of a particular clinical settingwill be done on the personnel (based on the protocol), instructionsfor CRF completion, submission of data procedures will be done beforesubject enrollment. Questions, as well as prompts and instructionalprocedures, will be maintained in a clear and concise manner.Instructions on data completion will be provided. The questions askedwill be framed in the positive perspective. The CRF will be designedto be in line with data flow (on the standpoint of the personcompleting the form). Consistent formatting (while making use of theexpected tool) will be emphasized. Data will then be collected in acoded form. Data in CRF will be maintained in an independent manner(devoid of reference and redundancy), with consistency in the orderthat is in place regarding the CRF choices. Data based on a similarmeasurement will not be collected in a location. Either raw data orcalculation based on raw data will be used and not both. Finally, theestablishment and maintenance of standard forms will be instigated.
DatabaseCreation and Validation
Databasedesign will take note of testing and set up of specific studies inthe bid to ensure to that a particular code is unique to anindividual study. The code will have to be in line the specificationof the user. Definition of the scope, methods used, research scope,problem identification, resolution, test information, and thecriteria for acceptance will be done, in line with the test plan.Identification of the usage of programming considered to be studyspecific will be done. PureO2 standards will be used in thedocumentation of programs. Code libraries will be utilized. All testswill be designed to be in conformance with set requirements regardingaccuracy and consistency. Validation of the screen for data entrywill be done at this point. Validation will then shift focus to thedatabase design of the protocol and its implementation. Databasedesign will be based on the standard data formats of PureO2.Specifications of the database will be at a minimum, taking note ofdesired variables.
Havingestablished the critical responsibilities in clinical trials,database, and CRF creation, addressing audits that will be conductedis in order. The audits will function majorly as a validation andverification tool.
Auditsduring Drug Development
Anaudit, according to Papp (n.d) is an independent exam (systematic)regarding activities related to trials, plus the relevantdocumentation. The aforementioned activities are aimed at carryingout evaluations as to whether tests were conducted, and whether datawas collected as per the laid protocol, regulations, and goodclinical practices. Audits will be done in the drug developmentproject because they offer assistance in the assessment of trialeffectiveness, identification of the safety, quality, and efficacy ofthe product under study (Papp, n.d). Additionally, the audits will beof critical importance in the assessment of conformance of a trial,as well as in the reduction of the observations that will be done.The audits that will be essential to drug development trials ofSimbarexwill include the following: Good Manufacturing Practices, GoodLaboratory Practices, and Good Clinical Practices.
Comparisonand Contrasting of the Audit Types
Allthe regulatory audit activities that will be undertaken are measuredin the aspect of how they will be carried out in practice. In such acase, observed pieces of evidence (with the absence of prejudice orbias), qualitative data and quantitative data utilized. Thedifferences between the regulatory audit types address the componentsthat each component measures. On that note, GMP takes note of theexamination of the manufacturing process of products. In such case,attention is paid to the sterility of the environment where themanufacturing process takes place. On the other hand, GLP activitiesare concerned with animal studies, which identify certain features ofoperations in the laboratory that are of a non-clinical nature. GCPregulatory action addresses the trial design, where attention is paidto the safety and efficacy level of a clinical product.
Thecomprehensive plan presented above is imperative, particularly in theclinical trials regarding the drug development of Simbarex,a drug discovered by PureO2. The plan is vital in offering ablueprint to the staff involved with the subsequent steps required inthe stepwise development Simbarex.In summary, the plan will shed light on quality assurance, security,administration, documentation, control health and safety protectioninformation, regarding the clinical trials of Simbarex.
IRBPolicy. (2013). Study Coordinator (SC) Responsibilities. RetrievedDecember 21, 2016, fromhttp://www.augusta.edu/research-admin/ohrp/study_coordinator_responsibilities.pdf
Meredith,J. (n.d). Data Management. The University of Delaware. (PPT).
Papp,K, J. (n.d). Auditing. The University of Delaware. (PPT).
PhRMA.(2015). Biopharmaceutical Research & Development: The ProcessBehind New Medicines. Retrieved December 21, 2016, fromhttp://phrmacdn.connectionsmedia.com/sites/default/files/pdf/rd_brochure_022307.pdf
Welch,M. (n.d). Pre-Study Visit and Initiation Visit. The University ofDelaware. (PPT).