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.

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.

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.

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).

scholarly journals The Disclosure Decision of Foreign Clinical Trials in China: Moderating Effects of Firms’ Contingencies

SAGE Open ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. 215824402110163
Author(s):  
Tariq H. Malik ◽  
Chunhui Huo
Keyword(s):  
Clinical Trial ◽  
Clinical Trials ◽  
Risk Taking ◽  
Academic Community ◽  
Moderating Effects ◽  
The Public ◽  
Industrial Enterprises ◽  
Unit Increase ◽  
Clinical Trial Results ◽  
Clinical Trial Activity

Result disclosure of clinical trial posts a conflicting logic between private secrecy and public interest. Despite ethical and legal requirements for disclosing clinical trial results, clinical trials’ sponsors tend to withhold the results. We explored the location, timing, and rationale behind the withheld clinical trial results. Based on the entrepreneurial orientation (EO) perspective, we propose that organizational EO contingencies moderate the disclosure decision. We used the completed clinical trial projects in China by foreign and domestic sponsors. First, we found that a unit increase in the sponsor’s experience can increase the disclosure about 1.01 times. Second, we found that industrial enterprises disclose results about 3.7 times more than universities do. Third, we found that foreign clinical trial projects in China tend to disclose 3.9 times more than domestic projects. We link these findings to two types of audience. First, we inform the academic community on the theory and empirics regarding risk-taking behavior in the biopharmaceutical industry’s clinical trial activity. Second, we address the general audiences concerned about the ethical and socioeconomic wellbeing of the public.

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.

Catastrophically Ill Children, Access to Unregistered Medical Interventions, and Trial Recruitment Needs

2018 ◽  
pp. 44-58
Author(s):  
Thomas D. Hartvigsson ◽  
Udo Schuklenk
Keyword(s):  
Clinical Trial ◽  
Ebola Virus ◽  
Medical Center ◽  
High Viral Load ◽  
Placebo Control ◽  
Trial Recruitment ◽  
Best Interest ◽  
Governmental Organization ◽  
Medical Interventions ◽  
The Face

This chapter discusses the case of a young girl infected by the Ebola virus during the epidemic outbreak in West Africa. She arrives alone to a medical center run by a non-governmental organization and is relatively well, but she has a high viral load and will with all certainty die within a week. This chapter argues that, in the face of imminent and certain death, it is permissible for the doctors at the medical center to use unregistered medical interventions, if they deem it to be in the best interest of the child. It further argues that they are permitted to do so without enrolling the child in a clinical trial, if the unregistered intervention is not scarce and the trial has placebo control groups.

Barriers to clinical trial accrual: Clinical trialists' perspectives.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e18156-e18156
Author(s):  
Edward S. Kim ◽  
Dax Kurbegov ◽  
Patricia A. Hurley ◽  
David Michael Waterhouse
Keyword(s):  
Clinical Trial ◽  
Clinical Trials ◽  
Cost Benefit ◽  
Trial Participation ◽  
Clinical Trial Participation ◽  
Eligibility Criteria ◽  
Contract Research Organization ◽  
The Public ◽  
Community Forum ◽  
Clinical Trial Accrual

e18156 Background: Oncology clinical trial participation rates remain at historic lows. There are many barriers that impede participation. Understanding those barriers, from the perspective of cancer clinical trialists, will help develop solutions to increase physician and site engagement, with the goal of improving accrual rates and advancing cancer treatment. Methods: Physician investigators and research staff from community-based and academic-based research sites were surveyed during ASCO’s Research Community Forum (RCF) Annual Meeting (N = 159) and through a pre-meeting survey (N = 124) in 2018. Findings and potential solutions were discussed during the meeting. Results: 84% of respondents (n = 84) reported that it took 6-8 months to open a trial and 86% (n = 81) reported that trials had unnecessary delays 70% of the time. The top 10 barriers to accrual identified were: insufficient staffing resources, restrictive eligibility criteria, physician buy-in, site access to trials, burdensome regulatory requirements, difficulty identifying patients, lack of suitable trials, sponsor and contract research organization requirements, patient barriers, and site cost-benefit. Respondents shared strategies to address these barriers. Conclusions: The current state of conducting clinical trials is not sustainable and hinders clinical trial participation. New strategies are needed to ensure patients and practices have access to trials, standardize and streamline processes, reduce inefficiencies, simplify trial activation, reduce regulatory burden, provide sufficient compensation to sites, engage the community and patients, educate the public, and increase collaborations. The ASCO RCF offers resources, available to the public, that offer practical strategies to overcome barriers to clinical trial accrual and has ongoing efforts to facilitate oncology practice participation in clinical trials.

Trifluoperazine (“Stelazine”) a Controlled Clinical Trial in Chronic Schizophrenia

1961 ◽  
Vol 107 (447) ◽  
pp. 250-257 ◽  
Author(s):  
W. J. Stanley ◽  
D. Walton
Keyword(s):  
Clinical Trial ◽  
Clinical Trials ◽  
Controlled Trial ◽  
Pernicious Anaemia ◽  
Chronic Schizophrenia ◽  
Mental Illnesses ◽  
Controlled Clinical Trial ◽  
Vitamin B ◽  
Uncontrolled Trial ◽  
New Compounds

So many new compounds are now being introduced for the treatment of psychiatric disorders that it is difficult for the clinician to assess the accuracy of the claims made for them. If a form of therapy is one hundred per cent. effective in a disease which was previously one hundred per cent. fatal, for example vitamin B12 in pernicious anaemia, the question of a controlled trial does not arise. But even the manufacturers do not claim such a degree of effectiveness for drugs advocated for the treatment of mental illnesses, and in addition the natural course of such illnesses is very variable, so that it is essential that clinical trials of these drugs should be controlled. Foulds (1958) has reviewed British and American clinical trials of drugs in psychiatry during the years 1951 to 1956, and has shown that the less controlled a trial, the more likely it is to result in a favourable report on the drug being tested, presumably because of bias on the part of the clinician. Forrester (1958), however, on the basis of a completely uncontrolled trial of Stelazine on only twenty-five patients, concluded that “the amount of improvement in a few cases was not sufficient to encourage the further use of the drug”.

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