Medical Ethics and Controlled Clinical Trials

1979 ◽  
Vol 88 (5_suppl) ◽  
pp. 99-106 ◽  
Author(s):  
Jerome O. Klein
Keyword(s):  
Clinical Trial ◽  
Clinical Trials ◽  
Informed Consent ◽  
Human Subjects ◽  
National Commission ◽  
Controlled Clinical Trial ◽  
Random Allocation ◽  
Controlled Clinical Trials ◽  
Potential Conflict ◽  
The Subject

The controlled clinical trial is a relatively new phenomenon; the first large clinical trial on evaluation of streptomycin in therapy of pulmonary tuberculosis occurred in 1946. In such a study, two or more groups of patients with similar characteristics are chosen by random allocation to receive one or more therapies. The essential ethical dilemma is based on the risk-benefit ratio of the new therapy. Ethical factors that must be considered in the design of controlled clinical trials include provision for informed consent, nature of alternate therapy, confidentiality of data, source of funding and potential conflict of interest, remuneration of subjects, criteria for ending participation of the subject, criteria for concluding the trial, compensation of injured subjects, compliance with institutional, municipal, state and federal regulations and provisions for special groups such as the fetus and pregnant woman, infants and young children, institutional patients and prisoners. Federal guidelines for research in specific areas are now available through the reports of the National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research. To date, commission reports include recommendations for research in fetuses and pregnant women and in children. Protection of the subject is best provided by the quality of the protocol, integrity of the investigator, valid informed consent, and review of the research program by an independent committee composed of scientists and consumers.

Analgesic Efficacy of Dextropropoxyphene and Dextropropoxyphene-containing Combinations: a Review

1984 ◽  
Vol 3 (1_suppl) ◽  
pp. 191s-220S ◽  
Author(s):  
W.T. Beaver
Keyword(s):  
Clinical Trial ◽  
Analgesic Efficacy ◽  
Controlled Clinical Trial ◽  
Controlled Clinical Trials ◽  
Congressional Hearings ◽  
Clinical Assay ◽  
The Subject ◽  
Minimum Criteria ◽  
Oral Doses ◽  
Mild Analgesics

Twenty years ago, as part of a review of the clinical pharmacology of mild analgesics (Beaver, 1965, 1966), I evaluated reports of those analgesic trials of dextropropoxyphene that appeared to satisfy the minimum methodologic requirements for a controlled clinical trial of analgesic efficacy. On reviewing reports of studies that have been published since then, I find little need to modify my evaluation of the efficacy of dextropropoxyphene that appeared in 1966, at least in respect to the effect of single oral doses: In summary, dextropropoxyphene (hydrochloride) is a mild oral analgesic which has proven superior to placebo in doses of 65 mg or more but which is of questionable efficacy in doses lower than 65 mg. The drug is definitely less potent than codeine: the best available estimates of the relative potency of the two drugs indicating that dextropropoxyphene is approximately 1/2-2/3 as potent. Likewise, dextropropoxyphene in 32-65 mg doses is certainly no more, and possibly less, effective than the usually used doses of aspirin or A.P.C. (aspirin/phenacetin/caffeine). In the interim, the efficacy of dextropropoxyphene has been the subject of a number of other critical reviews (Miller et al., 1970; Miller, 1977), commentaries (Kiplinger & Nickander, 1971; Lasagna, 1976), and even congressional hearings (Beaver, 1979; Moertel, 1979). More importantly, new controlled clinical trials involving dextropropoxyphene hydrochloride or napsylate have been reported, and some of these use more sophisticated design and analysis than those available in 1966. I will therefore discuss the results of those newer studies of apparently suitable scientific design that meet at least the minimum criteria for a valid clinical assay of analgesic activity (Beaver, 1965; Houde et al., 1965,1966; Wallenstein & Houde, 1975; Beaver, 1983), and I will comment on only a few of the studies included in my previous review (Beaver, 1966).

The Lugano Statements on Controlled Clinical Trials

1987 ◽  
Vol 15 (1) ◽  
pp. 2-22 ◽  
Author(s):  
A. L. Blum ◽  
T. C. Chalmers ◽  
E. Deutsch ◽  
J. Koch-Weser ◽  
A. Rosén ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Clinical Trials ◽  
Consensus Conference ◽  
Controlled Clinical Trial ◽  
Controversial Issues ◽  
Controlled Clinical Trials ◽  
Best Interest ◽  
The Public ◽  
Drug Companies ◽  
The Face

During a consensus conference in Lugano, Switzerland, 175 statements on controlled clinical trials were drafted by 47 representatives from academia, governmental registration agencies and industry in nine countries. Their opinion on these statements was similar to that of 47 ‘matched pairs’ who did not attend the conference. Thus, the opinion of participants and non-participants appears to reflect the general opinion of those currently involved in designing, conducting and analysing controlled clinical trials. The Lugano statements give answers to the following questions: Is the controlled clinical trial in a crisis? What is the motivation to perform controlled clinical trials? Is it possible for a physician participating in a controlled clinical trial to act in the patient's best interest? Is it possible to obtain truly informed consent in a controlled clinical trial? When is it ethical to withhold active treatment in a controlled clinical trial? What are the controversial issues in the design of a good controlled clinical trial? Is there a double standard with respect to efficacy and adverse drug reactions in controlled clinical trials? What are the alternatives to controlled clinical trials and when should they be performed? How can sponsor bias be minimized? How should an ethics committee decide whether a controlled clinical trial is Should? ethical registration agencies become directly involved in the planning and conduct of controlled clinical trials? Do the declarations of Tokyo and Helsinki facilitate the conduct of ethically valid controlled clinical trials? Is it possible to create an international standard for the conduct and regulation of controlled clinical trials? Why do messages from controlled clinical trials filter into medicine so slowly? Is it possible to bridge the gap between controlled clinical trials and clinical reality? What are the costs of doing and not doing controlled clinical trials? When should drug companies decide to start a trial programme with a specific compound? Is there public hostility against controlled clinical trials? If so, how can it be reduced? The respondents almost unanimously felt that controlled clinical trials are a must; the public must be told that progress in medicine depends on controlled clinical trials, that patients often benefit from participating in them and that the alternative, practising in the face of constant uncertainty, is worse than the possible disadvantages related to the conduct of the trial.

Use of Distance Function in Sequential Treatment Assignment for Prognostic Factors in the Controlled Clinical Trial

1980 ◽  
Vol 29 (1-2) ◽  
pp. 99-102 ◽  
Author(s):  
Damaraju Raghavarao
Keyword(s):  
Clinical Trial ◽  
Clinical Trials ◽  
Prognostic Factors ◽  
Distance Function ◽  
Sequential Treatment ◽  
Controlled Clinical Trial ◽  
Multivariate Methods ◽  
Controlled Clinical Trials ◽  
New Approach ◽  
Main Effects

In controlled clinical trials, the treatments are likely to be influenced by various prognostic factors, and while assigning treatments sequentially to the patients it is desirable to allot the treatments in such a way that the treatments are balanced over the main effects of prognostic factors and also on some or all interactions between the prognostic factors if the interactions are present. Efran (1971), Pocock and Simon (1975) and Freedman and White (1976) described some methods of balancing the treatments over the prognostic factors. In this paper, we shall describe a new approach in assigning the treatments using multivariate methods.

scholarly journals Controlled Clinical Trials with Doping Substances in Sports Law

2015 ◽  
Vol 46 (3) ◽  
pp. 827
Author(s):  
Erwin Deutsch
Keyword(s):  
Clinical Trial ◽  
Clinical Trials ◽  
Sports Medicine ◽  
German Law ◽  
Ethics Committee ◽  
Controlled Clinical Trial ◽  
Efficacy And Safety ◽  
Controlled Clinical Trials ◽  
Sports Law ◽  
Medical University

The research ethics committee of a German medical university recently faced a totally new problem. The department for sports medicine had asked the committee to approve a protocol for a controlled clinical trial about the efficacy and safety of doping substances in cycling. This article considers the difficulties of the German law on this matter.

scholarly journals “Include me if you can”—reasons for low enrollment of pediatric patients in a psychopharmacological trial

Trials ◽  
2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Larissa Niemeyer ◽  
Konstantin Mechler ◽  
Jan Buitelaar ◽  
Sarah Durston ◽  
Bram Gooskens ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Clinical Trials ◽  
Demographic Data ◽  
Autism Spectrum ◽  
Current Therapy ◽  
Future Research ◽  
Controlled Clinical Trial ◽  
Double Blind ◽  
Clinical Patient ◽  
Compulsive Disorder

Abstract Background Low recruitment in clinical trials is a common and costly problem which undermines medical research. This study aimed to investigate the challenges faced in recruiting children and adolescents with obsessive-compulsive disorder and autism spectrum disorder for a randomized, double-blind, placebo-controlled clinical trial and to analyze reasons for non-participation. The trial was part of the EU FP7 project TACTICS (Translational Adolescent and Childhood Therapeutic Interventions in Compulsive Syndromes). Methods Demographic data on pre-screening patients were collected systematically, including documented reasons for non-participation. Findings were grouped according to content, and descriptive statistical analyses of the data were performed. Results In total, n = 173 patients were pre-screened for potential participation in the clinical trial. Of these, only five (2.9%) were eventually enrolled. The main reasons for non-inclusion were as follows: failure to meet all inclusion criteria/meeting one or more of the exclusion criteria (n = 73; 42.2%), no interest in the trial or trials in general (n = 40; 23.1%), and not wanting changes to current therapy/medication (n = 14; 8.1%). Conclusions The findings from this study add valuable information to the existing knowledge on reasons for low clinical trial recruitment rates in pediatric psychiatric populations. Low enrollment and high exclusion rates raise the question of whether such selective study populations are representative of clinical patient cohorts. Consequently, the generalizability of the results of such trials may be limited. The present findings will be useful in the development of improved recruitment strategies and may guide future research in establishing the measurement of representativeness to ensure enhanced external validity in psychopharmacological clinical trials in pediatric populations. Trial registration EudraCT 2014-003080-38. Registered on 14 July 2014.

scholarly journals Immunogenicity and Safety of Inactivated Sabin-Strain Polio Vaccine “PoliovacSin”: Clinical Trials Phase I and II

Vaccines ◽  
2021 ◽  
Vol 9 (6) ◽  
pp. 565
Author(s):  
Anastasia Piniaeva ◽  
Georgy Ignatyev ◽  
Liubov Kozlovskaya ◽  
Yury Ivin ◽  
Anastasia Kovpak ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Clinical Trials ◽  
Phase I ◽  
Safety Profile ◽  
Neutralizing Antibody ◽  
Polio Eradication ◽  
Controlled Clinical Trial ◽  
Double Blind ◽  
Good Tolerability ◽  
Poliomyelitis Vaccine

Global polio eradication requires both safe and effective vaccines, and safe production processes. Sabin oral poliomyelitis vaccine (OPV) strains can evolve to virulent viruses and result in poliomyelitis outbreaks, and conventional inactivated poliomyelitis vaccine (Salk-IPV) production includes accumulation of large stocks of neurovirulent wild polioviruses. Therefore, IPV based on attenuated OPV strains seems a viable option. To increase the global supply of affordable inactivated vaccine in the still not-polio free world we developed an IPV made from the Sabin strains–PoliovacSin. Clinical trials included participants 18–60 years of age. A phase I single-center, randomized, double-blind placebo-controlled clinical trial included 60 participants, who received one dose of PoliovacSin or Placebo. A phase II multicenter, randomized, double-blind, comparative clinical trial included 200 participants, who received one dose of PoliovacSin or Imovax Polio. All vaccinations were well tolerated, and PoliovacSin had a comparable safety profile to the Placebo or the reference Imovax Polio preparations. A significant increase in neutralizing antibody levels to polioviruses types 1–3 (Sabin and wild) was observed in PoliovacSin and Imovax Polio vaccinated groups. Therefore, clinical trials confirmed good tolerability, low reactogenicity, and high safety profile of the PoliovacSin and its pronounced immunogenic properties. The preparation was approved for clinical trials involving infants.

scholarly journals Ethical implications of procedural or protocol adjustments to clinical research involving the participation of human subjects during the COVID-19 pandemic

2021 ◽  
Vol 11 (3-4) ◽  
pp. 181-195
Author(s):  
Anetta Jedličková
Keyword(s):  
Clinical Trials ◽  
Clinical Research ◽  
Human Subjects ◽  
Subject Matter Experts ◽  
Ethical Challenges ◽  
Wide Audience ◽  
Ethical Implications ◽  
The Subject ◽  
Research Professionals ◽  
Trial Participants

Abstract The current coronavirus disease 2019 (COVID-19) pandemic has led to essential adjustments in clinical research involving human subjects. The pandemic is substantially affecting most procedures of ongoing, as well as new clinical trials related to diseases other than COVID-19. Procedural changes and study protocol modifications may significantly impact ethically salient fundamentals, such as the risk-benefit profile and safety of clinical trial participants, which raise key ethical challenges the subject-matter experts must face. This article aims to acquaint a wide audience of clinical research professionals, ethicists, as well as the general public interested in this topic with the legal, ethical and practical considerations in the field of clinical trials during the COVID-19 pandemic and to support the clinical researchers and study sponsors to fulfil their responsibilities in conducting clinical trials in a professional way that does not conflict with any legal or ethical obligations.

Ethics in Clinical Studies: The Dilemma of very Young and Old

2021 ◽  
Vol 3 (2) ◽  
Author(s):  
Avisek Dutta ◽  
Avisek Dutta ◽  
Avisek Dutta
Keyword(s):  
Clinical Trial ◽  
Clinical Trials ◽  
Human Physiology ◽  
Informed Consent ◽  
Adverse Effects ◽  
Age Groups ◽  
The Elderly ◽  
Infantile Spasms ◽  
Care Givers ◽  
Improve Health

The objectives of the research are to percolate knowledge which can improve health and improve understanding of human physiology. Pervasive exclusion of children and elderly in clinical trials as is happening today is not justified. Children have different physiology and pharmacology from adults; often adverse effects are also different and specific. Diseases like neonatal hyperbilirubinemia, infantile spasms are very age specific. Elderly too, have age specific issues like dementias, malignancies, weakened systems and polypharmacy that make them a special cohort. Clinical trials in these age groups are essential so as to gather comprehensive data about a medication across all age groups. Informed consent is a challenge in both these groups. It can be remedied by obtaining consent from parents, or legally acceptable representative in case of children and care givers and/or LARs in case of the elderly. Oral assent from 7 to 11 years, and written assent from 12 to 18 years and in the elderly, along with consent from the LAR, parents, care givers as the case may be, forms the bedrock of good clinical trial ethics.

Increasing Health Literacy to Improve Clinical Trial Recruitment

2018 ◽  
pp. 94-108
Author(s):  
Saliha Akhtar
Keyword(s):  
Clinical Trial ◽  
Decision Making ◽  
Clinical Trials ◽  
Informed Consent ◽  
Health Literacy ◽  
Trial Recruitment ◽  
Negative Perception ◽  
Consent Forms ◽  
Clinical Trial Recruitment ◽  
And Training

Health literacy has been found to be linked to healthcare understanding and decision making. Therefore, it makes sense why individuals who do not understand clinical trials will be less likely to want to enroll in one. In fact, three major barriers found in the literature that prevent potential participants from enrolling in clinical trials include a distrust or negative perception, lack of understanding, and lack of accessible and affordable healthcare. Hence, there is a need to increase potential participants' healthcare understanding so that they can make the best healthcare decisions for themselves. Strategies suggested to help increase potential participants' health literacy include revising informed consent forms, utilizing culturally targeted statements, using a variety of material, and training investigative site personnel. These proposed strategies may help increase health literacy, which in turn could improve clinical trial recruitment. Furthermore, these strategies focus on different elements of health literacy and coupled together may bring the most improvement.

Telephone-based nursing intervention improves the effectiveness of the informed consent process in cancer clinical trials.

1996 ◽  
Vol 14 (3) ◽  
pp. 984-996 ◽  
Author(s):  
N K Aaronson ◽  
E Visser-Pol ◽  
G H Leenhouts ◽  
M J Muller ◽  
A C van der Schot ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Clinical Trials ◽  
Informed Consent ◽  
Cancer Patients ◽  
Intervention Group ◽  
Nursing Intervention ◽  
Informed Consent Process ◽  
Consent Process ◽  
Trial Participation ◽  
Oncology Nurse

PURPOSE Here we report the results of a randomized study undertaken to test the efficacy of a supplementary, telephone-based nursing intervention in increasing patients' awareness and understanding of the clinical trials in which they are asked to participate. METHODS During a 12-month period, 180 cancer patients who were approached to participate in a phase II or III clinical trial were randomized to undergo either of the following: (1) standard informed consent procedures based on verbal explanations from the treating physician plus written information (controls); or (2) standard informed consent procedures plus a supplementary, telephone-based contact with an oncology nurse (intervention). For purposes of evaluation, face-to-face interviews were conducted with all patients approximately 1 week after the informed consent process had been completed. RESULTS The two groups were comparable with regard to sociodemographic and clinical variables. Both groups had a high level of awareness of the diagnosis and of the nature and objectives of the proposed treatments. The intervention group was significantly (P < .01) better informed about the following: (1) the risks and side effects of treatment; (2) the clinical trial context of the treatment; (3) the objectives of the clinical trial; (4) where relevant, the use of randomization in allocating treatment; (5) the availability of alternative treatments; (6) the voluntary nature of participation; and (7) the right to withdraw from the clinical trial. The intervention did not have any significant effect on patients' anxiety levels or on rates of clinical trial participation. Patients reported high levels of satisfaction with the intervention. CONCLUSION The use of a supplementary, telephone-based nursing intervention is a feasible and effective means to increase cancer patients' awareness and understanding of the salient issues that surround the clinical trials in which they are asked to participate.

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