It is Time to Make a Move! Ensure the Safety and Overall Wellbeing of theHuman Subjects Involved in Clinical Research Dr. Smita Singh (Academic Head ACRI) Mr. Shaji Paulose (Head of Formulation, SPLIntroduction:-Subject/Trial Subject is an individual who participates in a clinical trial, either asa recipient of the investigational product or as a control.The clinical trial is incomplete without the participation of an eligible humansubject. It is known that Clinical trial is the heart and soul of the modern drugdevelopment process. It has become the necessity to evaluate the safety and efficacyof the drug in the human participant. Amidst the intangible benefits that we accruethrough these systematic and organized clinical trials, it is crucial and imperativethat we diligently address the issue of protection to all the human subjectsparticipating in the respective clinical trial. Many events and incidents occurred inthe past clinical trial processes have an impact on both the researcher and theparticipant involved in clinical trial. Therefore, the question remains, how can weensure the safety and overall well being of the human subjects?Ethical principles that guides safety in Clinical ResearchThere are established guidelines and processes that monitor and ensure the safetyof the human volunteers.1. According to Belmonte there are 3 ethical principles that guides theclinical researcha) Respect for personb) Beneficencec) Justice Patient autonomy or respect for the person is an important principle in the medical ethics; in actual practice, especially in the context of developing countries, this important principle is usually disregarded or misrepresented or only partially acknowledged..
2 .Role of Investigator, Clinical Research Coordinator and Other staff;a) The investigator should understand that clinical research, is not only valuablefor the society but it is also ethically challenging. It requires an able and adepthandling of both the science and human values.b) The investigator has to be aware of the tension that could arise as a result ofbalancing the science and protection to the subjectc) The investigator has to inform subject accordinglyd) Take an opinion from other members, physician who are involved in the clinicaltrial to minimize the risk to the subject3. Responsibility of IRB/IEC in assuring the safety of human subjectsAn IRB is defined as a committee which is responsible for the review, approval,disapproval, modification and suspension or termination of trial related to humansubjectIRB is responsible for:-a) Review of important documents like informed consent form, protocol,b) Investigator brochure update, Financial document and advertisementc) Review research to ensure that benefit outweighs the riskd) Review reports related to death, serious unexpected adverse event sent by theinvestigatore) Conducting periodic review of all the documents, benefits, risks and informedconsents etc.,Common Problems associated with IRB:- Advertisement not reviewed and approved prior to conduct of clinical trial. Investigator qualification like CV not reviewed Various document like protocol, Informed consent form not review prior to theconduct of clinical trial 4. Informed ConsentInformed consent is defined as “Subject willingness to participate in the clinicaltrial after being informed about all the aspects of the clinical trial’.It demonstrates that Person has freely given conformation without any coercion
Person knows that this is research but not a treatment Person has been given all the important and relevant information related to thetrialMust include important information:- Objective and purpose of the research Benefit and risk associated with the research Duration of the research Any alternative treatment available Can withdraw from the treatment Compensation of unexpected injury Common Problems associated with Informed Consent Consent may not correct Proper signature are not obtained Poorly written consent form Missing required elements Amended form is not signed 5. Subject protection in U.S:-There are different methods which are followed in the U.S to protect the rights ofthe study subject:-Office for Human Research Protections which came in existence in the year June18, 2000, has a considerable power over the conduct of clinical trials.The Office for Human Research Protections (OHRP) provides leadership in theprotection of the rights, welfare, and wellbeing of subjects involved in researchconducted or supported by the U.S. Department of Health and Human Services(HHS).OHRP helps ensure this by Providing clarification and guidance, Developing educational programs and materials, Maintaining regulatory oversight, Providing advice on ethical and regulatory issues in biomedical and social-behavioural research. In addition to inaugurating the OHRP, Education and training of clinicalinvestigators and IRB staff. Improved monitoring to quickly detect problems in
patient’s safety, and penalties of up to $250000 per clinical investigator and up to$1 million per institution for violations of patient protection agreements.6. Subject protection in developing countriesWith a population of more than a billion of people and prevalence of disease likecancer and HIV, and excellent pool of investigator, CRAand CRC, makes India anattractive location for foreign companies. Nevertheless, the subject enrolled inIndia is more vulnerable .Why?6.1 Poor public health and educational system in Developing countries:-Due to which the participant may not fully understand about the rights whileparticipating in the clinical trial6.2 Inadequate dissemination of information6.3 Unemployment:-The unemployed and people below poverty line choose to bepart of clinical trials to get free treatment6.4 Corruption in the public and private sectors.In the context of developing countries, informed consent was nonexistent till theConsumer Protection Act came into existence. Now, both doctors and patients arebecoming more aware about this concept, and patients are better informed of theirrights, safety and well being. Informed consent is very important before any medical treatment. Such consentcan be implied, as in the case of a general physician’s treatment, when physician istrying to administer any drug or to perform any surgical procedure. In developingcountries, where informed consent is infancy, most important elements of the trialsare hidden and particularly in hospitals they are expected to sign the Informedconsent form with a rider stating that they are willing for any kind of treatment.Hence, it is very significant that subject knows about all the important andrelevant information pertaining to the trial.6.5 Lack of facility and coordination among regulatory agencies In August 2008, according to a report there are: "Fewer than 40 ethics committeesin India are properly constituted and functioning” Ironically there is no proper linkage between Director Control General of Indiaand Ethics Committee which are the governmental and institutional level ofregulatory respectively .The DCGI fully depends upon the EC to implement theethical principles. The DCGI neither cares for the proper functioning of ECs nortake care of how the rules and regulations are implemented. It’s been 30 years ofEC in India but still there is no effective review process in India. This is the time tobreak the silence and improve the ethical challenges that India is facing today.
ConclusionThe clinical trial is done to produce knowledge about treatment efficacy by wellcontrolled experiment in groups of patients with the aim of promoting the rightsafety and wellbeing of the patients. It is very important for the participant tounderstand that every drug and treatment has its side effect. In order to achievethis, the investigator has to ensure that the respective information is passed on tothe participating human volunteers effectively in its complete form without unduebias. The benefit-risk ratio of every treatment is paramount in the conduct of anyclinical trial. Modern science cannot guarantee the benefit of clinical researchbecause the drug is in the process of trial. The expectation of patient in clinical trialis obvious. Therefore, improving communication skill between the investigator andthe subject has become mandatory for better informed consent. Enforcement of ethical standards in the profession and Communication forms thecore of the concept on informed consent.ReferenceJournal of the Forum for Medical Ethics Societyhttp://www.theheart.org/article/129765.dowww.crc.gov.myhttp://www.hhs.gov/ohrp/humansubjects/guidance/belmont.htmlhttp://www.hhs.gov/ohrp/Publication: Bulletin of the World Health Organization; Type: News Article DOI: 10.2471/BLT.08.010808http://www.medindia.net/indian_health_act/consumer_protection_act_and_medical_profession_doctor_patient_relationship.htm