Informed consent as viewed by patients participating in cardiology drug trial

Abstracts

FUNDAMENTO: Em ensaios clínicos, o Termo de Consentimento Livre e Esclarecido (TCLE) é fundamental para preservar a ética, mas pela sua complexidade ele pode não ser entendido completamente. Neste estudo, avaliamos o entendimento do TCLE pelo paciente. OBJETIVO: Abordamos a questão sobre o nível de compreensão dos pacientes em relação aos estudos baseados no Consentimento Informado. MÉTODOS: Convidamos participantes de pesquisa ambulatorial fases II, III e IV, com fármacos, para responder um questionário estruturado com 29 questões, tais como: por que aceitou participar? Leu o TCLE antes de assinar? Ao assiná-lo, estava certo de tê-lo entendido? Oitenta indivíduos (20 mulheres e 60 homens) compareceram, num universo de 106 pacientes. As variáveis de cada questão foram consideradas por frequência de ocorrência. A comparação entre as médias entre os grupos foi realizada pelos testes t de Student ou Wilcoxon; e para associações, o Qui-quadrado ou Razão de Verossimilhança, ou teste exato de Fisher. RESULTADOS: A média das idades foi de 58,7 ± 9,3 anos. Das motivações para participar da pesquisa, 66,2% apontaram seu próprio benefício; 42,5%, o bem da ciência; 25,0% alegaram atender a um pedido de seu médico; 50% não entenderam corretamente o TCLE; e 32,9% sequer o leram, mas o assinaram. Dentre os que receberam placebo após a randomização (n = 47), 66,7% não entenderam o significado deste termo. Houve forte correlação entre o não entender o significado de placebo com a escolaridade (p = 0,02), evidenciando que quanto menor o nível de instrução, menor este entendimento. CONCLUSÃO: O TCLE é pouco compreendido pelos pacientes e para alguns deles a confiança no médico teve impacto na decisão de participar do ensaio clínico com fármaco, havendo também influência do nível de instrução dos sujeitos no entendimento do termo "placebo".

Ensaios clínicos controlados aleatórios como assunto; ética

FUNDAMENTO: En ensayos clínicos, el Formulario de Consentimiento Informado (FCI) es fundamental para que se preserve la ética, sin embargo por su complexidad él puede no comprenderse completamente. En este estudio, evaluamos la comprensión del FCI por parte del paciente. OBJETIVO: Abordamos la cuestión sobre el nivel de comprensión de los pacientes respecto a los estudios basados en el Consentimiento Informado. MÉTODOS: INVITamos a los participantes de investigación clínica fase II, III y IV con fármacos para responder un cuestionario estructurado con 29 cuestiones, tales como: ¿Por qué aceptó participar?¿Leyó el FCI antes de firmarlo?¿Al firmarlo estaba seguro de haberlo entendido? Ochenta individuos (20 mujeres y 60 varones) comparecieron, en un total de 106 pacientes. Las variables de cada cuestión se llevaron a cabo por frecuencia de ocurrencia. La comparación entre los promedios entre los grupos se realizó mediante las pruebas t de Student o Wilcoxon; y para asociaciones, el Chi-cuadrado o Razón de Verosimilitud, o prueba exacta de Fisher. RESULTADOS: El promedio de las edades fue de 58,7 ± 9,3 años. De las motivaciones para participar en la investigación, el 66,2% señaló su propio beneficio; un 42,5%, el bien de la ciencia; un 25,0% alegó atender a una petición de su médico; el 50% no comprendió correctamente el FCI; y un 32,9% tampoco leyó el formulario, pero lo firmó. Entre los que recibieron placebo tras la randomización (n = 47), un 66,7% no entendió el significado de este término. Hubo una fuerte correlación entre las personas que no entendían el significado de placebo con la escolaridad (p = 0,02), evidenciando que cuanto menor era el nivel de instrucción, menor era la comprensión. CONCLUSIÓN: EL FCI es poco comprendido por los pacientes y para algunos de ellos la confianza en el médico tuvo impacto en la decisión de participar en el ensayo clínico con fármaco, habiendo también influencia del nivel de instrucción de los sujetos en la comprensión del término "placebo".

Ensayos clínicos controlados aleatorios como asunto; ética

ORIGINAL ARTICLE

^IInCor-Instituto do Coração do Hospital das Clínicas da Faculdade de Medicina da USP

^IIEscola de Enfermagem da USP, São Paulo, SP - Brazil

Mailing address

ABSTRACT

BACKGROUND: In clinical tests, the Informed Consent is critical to preserve the ethics, but due to its high complexity level, it cannot be fully understood. This study assesses the Informed Consent as viewed by patients.

OBJECTIVE: We addressed the issue of what do patients understand about the studies based on the IC.

METHODS: We invited participants of outpatient clinical drug trials phase II, III and IV to answer a questionnaire with 29 questions, such as: why have you accepted to participate? Did you read the Informed Consent before signing it? By signing it, were you sure you have fully understood it? Eighty individuals (20 women and 60 men) showed up, from 106 patients. The variables of each question were considered as often as they appeared. The comparison of the averages among the groups was made by t tests of Student or Wilcoxon; and for associations, Chi-square or Likelihood Ratio, or Fisher's exact test..

RESULTS: Ages averaged 58.7 ± 9.3 years. Concerning their reasons to taking part in the survey, 66.2% pointed out their own benefit; 42.5%, for science's sake; 25.0% claimed they were doing so at their doctor's request; 50% did not understand the Informed Consent properly; and 32.9% did not read it, but signed it. Among those who were administered placebo after randomization (n = 47), 66.7% did not understand the meaning of the informed consent. A strong correlation between failure to understand the meaning of placebo with literacy level (p = 0,02) was verified, which is an evidence that the smaller is the literacy level, the smaller is the understanding level.

CONCLUSION: The Informed Consent is poorly understood by patients and for some of them, trusting a doctor affected their decision in taking part in the clinical trial with drugs. Their literacy level also influenced their understanding of the term "placebo".

Key words: Randomized controlled trials as topic; informed consent; comprehension; ethic.

Introduction

Trials with human beings are still critical, mainly in cardiology, as new drugs are usually for continued use. In Brazil, there was an increase in the number of sponsored trials, after the Brazilian Health Council authorized trials with human beings (CNS/MS 196/96)¹. Then, the Informed Consent was introduced. The Informed Consent is a document that contains information on the study and the responsibilities involved. The Informed Consent is often taken for granted. Sometimes it is even viewed as a disclaimer². Investigators may also be faced with a conflicting double role (doctor/researcher)^3,4, besides the power he has on the patient, taking into account the asymmetrical relationship among them^5,6.

One of the challenges posed in the 21^st century is not allowing the power of technology to gain importance over the respect to people dignity, mainly in developing countries⁷. Cardiology presents an expressive number of studies in this area, which explains why we seek to assess, in these first 10, 12 years after the establishment of Ethics Committees in Brazilian hospitals, how the individuals participating in scientific trials view a study, starting with the Informed Consent, and which explanation given by those who develop the trial. We conducted this study by means of cross-sectional descriptive exploratory research, with qualitative and quantitative approach.

Methods

The study was conducted in a public hospital in the city of São Paulo, specialized in cardiology and educational and research activities. After the approval of the Ethics Committee for research in an institutional database of patients participating in clinical trials, we found phase II, III and IV of drug studies, conducted in specialized outpatient care from 2002 to 2006, with or without placebo. Then, we selected all clinical trials from 6 , which we deemed appropriate to these characteristics, which were conducted in that hospital in that period. In order to participate, the individuals should have used placebo at least in the washout period, or in comparison to the drug under trial, and they should have been randomized in the trial.

Data collection instrument

The data were collected from interviews and reference to patients' files. As there is no specific form to assess the interpretation of an Informed Consent, we drew on questions that could assess the understanding of the content and meaning of words. The questionnaire contained 29 items, including general information data and specific multiple-choice questions and open-ended questions. Besides the general characteristics of individuals, we assessed their literacy level considering the following levels:

1) elementary/middle education;

2) high school; or

3) higher education, considering complete or incomplete studies. As to the specific understanding matter, both in the trial itself and in the use of placebo, the individuals were submitted to an objective questionnaire which included the following questions and options:

I) Who invited you to take part in this trial? Options: 1 - researcher; 2 - another patient; 3 - nurse; 4 - secretary; 5 - others;

II) Was the inviter a contributing factor for you to take part in the trial? Options: Yes or No;

III) How were you contacted to come to the hospital to take part in the trial? Options: 1 - by telephone; 2 - in person; 3 - others;

IV) Were you told that you would take part in a trial? Options: Yes or No;

V) Why did you accept to take part in the trial? Options: 1 - for science's sake; 2 - for my own benefit; 3 - because my doctor asked me to; 4 - because my doctor told me it would be good to me; 5 - because I feared not being assisted or losing my turn; 6 - because this is a public hospital; 7 - other.

The following were yes or no questions: VI) Were you informed about how important is the trial? VII) Of the potential risks and distresses that could arise due to the trial? VIII) Of treatments other than those included in the trial? Then, the questions were specifically directed to the Informed Consent: IX) When you decided to take part in the trial, did you sign any documents? X) Have you read the document before signing it? XI) Did you discuss the Informed Consent with the researcher? XII) Upon signing the Informed Consent, were you sure you have understood what the Informed Consent explained? They also answered to the following: XIII) If you were not sure of having understood it, what did you do? Options: 1 - you signed it even though you had not understood it; 2 - you asked explanation from the researcher ; 3 - other.

Then, the following yes or no questions were asked: XIV) Were you provided with a copy of the document? XV) Did you understand what "placebo" meant?

Then, an open ended question was made: XVI) What did you understand (or not)?

Then, the following yes or no questions were asked: XVII) Did you know you could take a pill with no effect for some months? (this question applied only to those patients administered placebo as a treatment); XVIII) Was it important for you to have taken part in a trial? Why? (free answer).

Statistical analysis

The quantitative variables were analyzed in terms of averages and standard deviations. The classifying variables were presented in tables containing absolute (n) and relative (%) frequencies.

In order to check whether there was association among some issues, the potential associations of these variables were analyzed through Student's t test, Chi-square or Likelihood Ratio, or Fisher's exact test, as applicable⁸. The statistical analysis was conducted with the support of the software SPSS version 15.0 (SPSS Inc., EUA). The values p < 0,05 were considered statistically significant for the analysis. As for the analysis of descriptive data obtained through direct contact of researchers with patients by means of open-ended questions, we used the content analysis proposed by Bardin⁹.

Focal group

In order to complement the data obtained through the qualitative and quantitative survey, especially to confirm patients' understanding of the term "placebo", we decided to build a focal group, once it is widely used technique intended to obtain data from previously planned discussions, where participants express their experiences, values, beliefs, attitudes and social representations on specific questions¹⁰. This technique is particularly appropriate when the interviewer has a number of open-ended and multiple-choice questions and wishes to encourage participants to explore a subject of extreme importance for them, in their own words and following their own priorities¹¹. We also sought to get answers that could easily explore and clarify opinions and viewpoints by speaking their language, considering their perceptions on the subject, as compared to others' views¹².

Results

The studies in which patients participated were high blood pressure and ischemic heart disease treatments. Individuals included in the clinical trials likely to be located and those who would easily accept this survey were selected. Eighty individuals were interviewed in the second half of 2006, from 6 months to 4 years after the completion of the trial in which they participated to the interview. Out of these patients, 69 participated in studies with placebo, or in a washout phase, or as a comparison to the drug under trial during the active treatment phase-which means that the term "placebo" was written in the Informed Consent. From the individuals, 47 had effectively received placebo in the active treatment phase - the general characteristics of the patients are on Table 1. An expressive number of individuals-51 (63.8%)-did not completed elementary/middle education or were even self-declared as illiterate. Most of them (52.5%) were not engaged in any professional activity. Table 2 shows the answers concerning the patients' reason to taking part in the clinical trial. It was crystal clear in patients' perception that they feel benefitted by taking part in a study, as 66.2% stated they had taken part for their own benefit.

Data related to the Informed Consent

Specifically concerning the Informed Consent (Table 3), 25.0% of individuals declare they have not received any type of information on the importance of the trial to which they were invited to take part, and almost half (42.5%) was neither informed of the risks nor the distresses involved. Worth of note is that the guarantee of confidentiality, which is critical during a trial, was not known by almost half of individuals (47.5%). On the other hand, only 67.1% have read the Informed Consent before signing it, and 52 individuals (65.0%) did not discussed it with the researcher. When asked about their understanding of the information contained in the Informed Consent, 50.0% of individuals did not understand the content or the information explained by the researcher. More importantly: even though they did not understand the information contained in the Informed Consent, 39 individuals (97.5%) signed it.

The meaning of "placebo"

When the 69 individuals were asked about what they understood from "placebo", 46 interviewees (66.7%) declared they have not learned about it. When asked about what they understood from it, 47.8% confirmed they did not know what "placebo" means and 18.8% have misleading beliefs as to its meaning. Therewith, we observe that only 20.3% of interviewees understood its meaning. We also observed that 13.0% of participants did not remembered the information they read when the interview was applied. As to the associations among the characteristics of individuals and their answers on the term "placebo", Chart 1 shows that the literacy level was not necessarily a contributing factor to the patients' understanding (p = 0.02).

Discussion

There are several aspects related to the individuals' perception while taking part in a clinical trial. This study confirms and brings forward key concepts to implement Informed Consent application strategies to those patients with lower literacy levels, especially the ones coming from public institutions. As to the educational level, most interviewees were illiterate or had dropped out elementary/middle school (63.8%). Souza¹³ observed similar results, in data collected from 793 patients invited to take part in clinical trial protocols conducted in public and private institutions. In this study (53% males, averaged 58.2 years of age), the prevailing literacy level among the 444 individuals (96%) from public institutions was similar to our sample. Therefore, this is a sign of the high educational debt in Brazil, where 47% of Brazilians, aged between 14 and 64, did not complete grade 8 of middle school¹⁴. Among the ones who completed it, only 11% are considered fully literate¹⁵. That impacts in the clinical trial, once many patients may not be able to read and understand the Informed Consents¹⁶. According to Resolution 196/96¹, the informed consent must be applied to the individuals participating in the trial, which often requires reading it aloud, explaining verbally and interacting, by means of dialogues, with the doctor delivering the Informed Consent. That applies mainly to outpatient studies, once there is sufficient time for researchers to dedicate to this application. In a study on acute myocardial infarction requiring immediate treatment, for instance, something different occurs: in this circumstance, more often than not, information are verbal and not read, at least by the patient. Because of that, and to the natural inhibition of those with lower literacy level, such individuals will hardly let the others know they do not understand what they are reading, that it, they read but fail to understand.

This study could successfully detect the problem of misleading interpretation, irrespective of which questionnaire was used. Such a distressful situation is not only restricted to our country and culture: A systematic review of 12 studies, conducted by Flory and Emanuel¹⁷, revealed that participants with high level of literacy or reading skills presented significant superior understanding levels (p < 0,05). In our study, as to the reasons to participate, we observed that most of them (66.2%) did that for their own benefit, and for the science's sake (42.5%). Comparing the data of this study with those of Sakaguti¹⁸, we found that, although the author has studied 50 individuals assisted in the units managed by the City Office of Health and the Dentistry School of the University of São Paulo, the results agree on the main reasons why the individuals accepted to take part in the clinical trials. In this study, 68% of individuals accepted to take part for their own benefit, 18% for science's sake and 2% upon their doctor's request. Another aspect stands apart: from a study with 35 patients participating in clinical trials sponsored by the pharmaceutical industry in oncology centers in Mexico, 46% of patients accepted to take part in the trial and signed the informed consent to have access to the treatment, 29% did so to release the doctors and the hospital from any accountabilities none of them thought the informed consent would serve to protect them as patients¹⁹. Also in our study, 25% of individuals accepted the invitation to take part in the trial upon their doctor's request or recommendation. The words of a doctor may change the course of life or exercise great influence on a patient's²⁰ decision, not to mention the permanent possibility of conflicts of interest in trials sponsored by the pharmaceutical industry^21,22.

Data related to the Informed Consent

There is a huge variation in patients' understanding of the Informed Consent, which may also be due to the various information provided by investigators. In our study, 25% of individuals declare they have not received any type of information on the importance of the trial, and almost half (42.5%) was neither informed of the risks nor the distresses involved. The same is true as to other existing treatments - 66 individuals (82.5%) did not receive such information. These individuals may have had difficulties in recalling this information, due to the interval between the trial and the interview. Then, an effective communication between the doctor and the patient is extremely important to deliver effective information upon assigning an Informed Consent. Thus, we may infer that the way through which the doctor communicates with patient influences their judgment on the risks, benefits and barriers to take part in the study²³.

Professionals often consider the informed consent a statutory requirement, but not a means to afford autonomy to the individuals²⁴. The complex information found in the Informed Consent, as well as the technical terms and the excessive number of pages, are contributing factors to prevent it from being properly understood^25,26. Although our study has not analyzed the terms used in the performance of clinical trials, literature is unanimous in recognizing the "literary abilities" of individuals as a determining factor in the understanding process. Participants with insufficient "literary abilities" understand a minimum quantity of information contained in the Informed Consent²⁷.

Insights on the term "placebo"

As to the meaning of "placebo", the specific question was asked to 69 (87%) individuals-from 80-whose trials included the word "placebo" in the Informed Consent. When asked about they have understood or not from the meaning of placebo, almost half of them confirm they did not understand the meaning of this word (47.8%) or hold misleading beliefs as to its meaning (18.8%). Therewith, we observe that only 20.3% of interviewees understood its meaning. Moodley et al²⁸ interviewed 334 individuals from 4 to 12 months after a study conducted in South Africa to test the vaccine for influenza. Data reveal that, although 91% declare to have understood the explanation about study, 81% did not understand the meaning of the word placebo.

Final insights and constraints

The Informed Consent is still poorly understood and for individuals, trusting their doctor is critical to their decision to take part in a clinical trial with drugs. We could also verify the influence of the literacy level of individuals in understanding the term "placebo", strongly suggesting that some words and expressions presented in the Informed Consent are still very complex and fail to fulfill the need they are supposed to. A wide range of strategies may be used to improve participants' understanding, but these are not being tested yet. In the systematic review conducted by Flory and Emanuel¹⁷, who addressed the interventions used to improve participants' understanding of the informed consent, some methods seem to be more effective than the others in this process.

We a in recent process of application of a structured Informed Consent. The assessment made in this study focused on sponsored trials, in which informed consents are usually more structured than those of independent trials. On the other hand, a huge number of pieces of information prevent the participants from properly understanding the trial. Such difficulties of understanding, however, are not only found in Brazil. Rather, they are found in many other countries. Lastly, the sample of 80 patients may be considered small to get accurate information on this subject. It is also true that the questionnaire applied, which is not a specific one, may pose constraints to the study. Nevertheless, specific questions on and Informed Consent understanding were direct and objective. Despite these constraints, this information has never been introduced before, and we conducted a quantitative analysis with this material. The confirmation of interpretation data by the individuals taking part in the survey, through other interviewing techniques, will certainly bring greater contribution to corroborate these results, which is included in a future analysis for this study.

Potential Conflict of Interest

No potential conflict of interest relevant to this article was reported.

Sources of Funding

There were no external funding sources for this study.

Study Association

This article is part of the thesis of doctoral submitted by Silmara Meneguin, from Incor - FMUSP.

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Informed consent as viewed by patients participating in cardiology drug trial

Silmara Meneguin^I; Elma L. C. P. Zoboli^II; Raquel Z. L. Domingues^I; Moacyr R. Nobre^I; Luiz A. M. César^I

Publication Dates

• Publication in this collection
  22 Sept 2010
• Date of issue
  Jan 2010

History

• Received
  27 Jan 2009
• Accepted
  23 June 2009
• Reviewed
  2090