[Clinical trials in "developing" countries: is there a special "Third World" ethic?].

David J Rothman

Home/Archive/PubMed

PubMed · 14997587

[Clinical trials in "developing" countries: is there a special "Third World" ethic?].

David J Rothman

View original source ↗Export metadata ↓

Abstract

With increasing frequency, clinical trials are carried through in countries of the "third world". In particular, recent studies aimed at establishing the efficacy of new AIDS therapies, or AIDS vaccines, applied lower ethical standards than those formulated by the Declaration of Helsinki of the World Medical Association, and accepted in the US and internationally,--although American researchers and institutions were involved in these studies. The paper reconstructs the controversies following the publication of these studies, and analyses the conditions for the existence of such double standards of research ethics. Particular attention is given to the concept of informed consent and the difficulties to put it into practice in different cultural contexts.

Explore related subjects

AIDS Vaccines Acquired Immunodeficiency Syndrome Clinical Trials as Topic Developing Countries Ethics, Research Humans Research Comparative Study English Abstract Journal Article

Keep this discovery

Explore connections, maps & timelines

BibTeX RIS

David J Rothman. 2003. [Clinical trials in "developing" countries: is there a special "Third World" ethic?].. https://pubmed.ncbi.nlm.nih.gov/14997587/

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related citations

PubMed2025

Increased immunogen valency improves the maturation of vaccine-elicited HIV-1 VRC01-like antibodies.

Antibodies belonging to the VRC01-class display broad and potent neutralizing activities and have been isolated from several people living with HIV (PLWH). A member of that class, monoclonal antibody VRC01, was shown to reduce HIV-acquisition in two phase 2b efficacy trials. VRC01-class antibodies are therefore expected to be one component of an effective HIV-1 vaccine elicited response. In contrast to the VRC01-class antibodies that are highly mutated, their unmutated forms do not engage HIV-1 envelope (Env) and do not display neutralizing activities. Hence, specifically modified Env-derived proteins have been designed to engage the unmutated forms of VRC01-class antibodies, and to activate the corresponding naïve B cells. Selected heterologous Env must then be used as boost immunogens to guide the proper maturation of these elicited VRC01-class antibodies. Here we examined whether and how the valency of the prime and boost immunogens influences VRC01-class antibody-maturation. Our findings indicate that, indeed the valency of the immunogen affects the maturation of elicited antibody responses by preferentially selecting VRC01-like antibodies that have accumulated somatic mutations present in broadly neutralizing VRC01-class antibodies isolated from PLWH. As a result, antibodies isolated from animals immunized with the higher valency immunogens display broader Env cross-binding properties and improved neutralizing potentials than those isolated from animals immunized with the lower valency immunogens. Our results are relevant to current and upcoming phase 1 clinical trials that evaluate the ability of novel immunogens aiming to elicit cross-reactive VRC01-class antibody responses.

AIDS Vaccines↗

PubMed2015

New approaches to HIV vaccine development.

Development of a safe and effective vaccine for HIV is a major global priority. However, to date, efforts to design an HIV vaccine with methods used for development of other successful viral vaccines have not succeeded due to HIV diversity, HIV integration into the host genome, and ability of HIV to consistently evade anti-viral immune responses. Recent success in isolation of potent broadly neutralizing antibodies (bnAbs), in discovery of mechanisms of bnAb induction, and in discovery of atypical mechanisms of CD8T cell killing of HIV-infected cells, have opened new avenues for strategies for HIV vaccine design.

AIDS Vaccines↗

PubMed2007

Analysis of antiretroviral immunotherapy trials with potentially non-normal and incomplete longitudinal data.

For many HIV-infected patients, use of antiretroviral therapy (ART) results in a sustained suppression of plasma viral load to undetectable levels. However, due to lack of antigenic stimulation, this may also result in a gradual loss of cell-mediated immune (CMI) responses that help control HIV infection. In concept, augmenting ART with periodic administrations of an HIV vaccine that boosts CMI responses could enhance control of viral replication. Researchers are designing 'antiretroviral immunotherapy' (ARI) trials to test this hypothesis. In a typical ARI trial, HIV-infected patients with sustained viral suppression will receive inoculations of an experimental HIV vaccine or a placebo, and subsequently stop taking their antiretroviral drugs. The goal is to assess whether plasma viral loads during the ART interruption phase are generally lower in the vaccine group. Assessment of a vaccine effect will be challenging if some subjects resume ART or drop out before the end of the treatment interruption phase. To tackle this 'missing' data problem and potential non-normality of the viral loads in ARI trials, we propose a two-step approach: multiple imputation of the missing values followed by use of the Wei-Lachin method with Wilcoxon scores. We use a numerical example and extensive simulations to illustrate the robustness and power advantages of our proposed method compared with other methods for incomplete longitudinal data, including REML, weighted GEE, last observation carried forward, and 'worst-rank' methods. Our proposed method is general enough for the robust analysis of longitudinal data in other therapeutic areas as well.

AIDS Vaccines↗