This study is a review of the article by The Solvd Investigators (1991) entitled: “Effect of enalapril on survival in patients with reduced left ventricular ejection fractions and congestive heart failure”. The abstract of the article is specific and offers a comprehensive summary of the article thus giving the reader an opportunity to review the contents of the study. Since the article sought to study the impact of enzyme inhibitor, enalapril, on the death or hospitalization of patients with ejection fractions and congestive heart failure, placebo or enalapril was administered to the patients at random in a double blind trial. The abstract is decipherable and excellently organized into the headings: background, methods, results, and conclusions, which briefly discuss the content without being verbose.
Though the article is credible, it lacks a clearly defined hypothesis. Instead, the researchers decided to state the hypothesis under statistical analysis in the methods section. The hypothesis for the study was that the administration of enalapril would decrease the rate of death. This is a poor way of indicating the hypothesis as the reader ought to be aware of the supposition being tested right from the content of the introductory section to acquire an early grasp of the study for easy comprehension. Moreover, rather than giving the aims of the study in a separate and apparent section, the investigators chose to incorporate a couple of them within the background of the article, which is a poor means of representing them.
One of the listed aims is the primary aim that affirms that the goal of the two trials undertaken in the study was to examine the impact of enalapril on death rate. The second one contains the key aims, which ascertain that the article sought to explore the influence of therapy on hospitalization for chronic heart failure, the occurrence of myocardial infarct, death attributable to particular causes, and a combined assessment of mortality and morbidity anchored in information from both tests. In this regard, the aims listed in the article clearly define the rationale behind the study. Irrespective of the absence of an excellently represented hypothesis, the article clearly defines the objective of the study as the examination of the effectiveness of either placebo or enalapril. The key aims are presented in a lengthy and unclear manner that could cause confusion in the readers or make them lose the morale to read on.
The hypothesis and aims indicated in the article are in line with the referred literature, which makes it easy for all the stakeholders in the healthcare system to comprehend with the purpose of making improvements where necessary. Implied within the hypothesis is the supposition that a causal connection will arise between the independent and dependent variable. That is, treatment with enalapril will result in reduced mortality amid patients with congestive heart failure and ejection fractions. Though this could appear as a simple supposition, its being established to be spot on resulted in imperative implications and recommendations for new approaches in a bid to enhance the quality of care. Essentially, the researchers proved the validity of the proposition that the incorporation of enalapril within conventional treatment methods will result in considerable reduction of mortality and stay in the hospital for patients with low ejection fractions and coronary failure. Possibly the most important aspect concerning the hypothesis is that it is evidently testable with the instruments developed for the research. From the hypothesis, major lessons can be learned and ideas inclined toward novel treatment approaches may be developed to benefit the patients.
Sample Size and Type
It is evident from the article that the patients with chronic heart failure, who formed the sample size, were chosen through random sampling at 83 health facilities associated with 23 organizations in the US, Belgium, and Canada. Patients with chronic heart failure, as well as ejection fractions, of no more than 0.35 and who were on treatment with other medications apart from angiotensin-converting-enzyme inhibitors qualified for selection in the research. Patients with congestive heart failure were disqualified from taking part in the study if they were more than 80 years old or showed signs of hemodynamically severe valvular illness that necessitated surgical operation, unstable angina pectoris, angina considered to call for revascularization practices, or earlier myocardial infarction. The patients were also ineligible if they had advanced pulmonary illness, serum creatinine of a level over 177 μmol/L, or any ailment that may considerably decrease lifespan or hinder contribution in long-standing assessment. The overall sample for the study was 2569 patients.
The sample size for the study is representative as the investigators had a well grasp of the population for the study and employed excellent selection criteria. In the study, the investigators chose to gather data regarding the effectiveness of either placebo or enalapril in the reduction of mortality in patients with ejection fractions or chronic coronary failure. The biggest challenge for the investigators was in the establishment of an approach of randomly choosing individuals from the population of the study with respect to the set eligibility criteria. The researchers came up with a huge sample in which they made commendable efforts to choose patients who could offer perfect generalization of the outcomes of the study. Since ensuring that a sample is actually representative in an exceedingly difficult task, the researchers indubitably devoted much of their time and finances in coming up with such a huge sample (Rothman, Gallacher, & Hatch, 2013).
The random type of sampling used by the researchers appears invalid. This could be attributed the fact that it took much time to realize (from 1986 to 1989) and gather required data, the amount of funds spent in the progression of the study is definitely overwhelming, and there was a high chance for bias to arise in the selection of the sample to take part in the study. Even with researchers’ intention to provide an unbiased outcome in the sampling progression, bias is bound to happen in random sampling due to such things as personal prejudice (Muchnik, Aral, & Taylor, 2013). To make sure that no bias arises in the process of sampling, the researchers may be required to choose a very broad sample and employ a different technique instead of the random approach, which might be impossible because of the issues of time and financial limitations.
Design of the Study
The quantitative research design employed in the article is the randomized, double blind technique where treatment with both placebo and enalapril was carried out. In the placebo controlled approach, the mere realization that an additional intervention was made might just yield an evident gain, regardless of the inherent advantages of the intervention. The major reason behind concealing the distinctiveness of the treatment extended past just the trials as the effectiveness of the different medications was being compared with the objective of making sure that the extent of the reaction variable was not in any way influenced by identification of the specific medicine administered. If the researchers had failed to double blind the treatment approaches effectively, they would have created a chance for the convictions or anticipations of the participants or the investigators to vex the study (Hernán, Hernández-Díaz, & Robins, 2013).
The major benefit by the carrying out of a double blind trial is that it generated confidence that the dissimilarities between the placebo and enalapril are real because the views of the caregivers, patients, and researchers were not factored in the findings. In this regard, the use of a double blind trial offered an unbiased approach that presented a precise idea of the effectiveness of the medications (McMurray et al., 2014). Nonetheless, the outcomes of the double blind trial cannot be considered successful. This is because the treatment approach resulted in the absurdity that such an efficient investigational treatment was not backed by best evidence (Boot, Simons, Stothart, & Stutts, 2013).
In the study, randomization was undertaken through the application of a computer-created allotment plan that held 16 patients at a time and stratified with respect to the health institution under consideration. The use of computer played a vital role in the eradication of bias that would have otherwise arose if a researcher undertook the initiative. The administration of the placebo or enalapril was initiated at either 2.5 or 5 mg two times in a day based on the health situation of the patient and the views of the medical professionals taking part in the study. Titration of the dosage was undertaken to a level of not more than 10 mg two times each day where the patient did not develop suggestive hypotension or deterioration of nephritic function. Reliance on the views of the health professional rather than the investigators ensured that the most excellent perspective was employed to minimize chances of error and bias. For every hospitalization case, the chart of the patient was evaluated by a health professional blinded to the medication administered with the aim of establishing the diagnosis. In this research, it was very beneficial to employ unbiased and reliable views, particularly because the investigators sought valuable outcomes to guide medical practices concerned with the improvement of the quality of care. Excellent measurement and deliberation approaches were employed in the research to assist in the enhancement of the validity and accuracy of the findings or results.
(The Solvd Investigators, 1991, p. 297)
In the study, 2.5 mg of enalapril was at first administered two times in a day in a single-blind approach for 2 to 7 days with the intention of recognizing the patients who may not put up with even small dosages of the medication for a short time and the ones who were incapable of adhering to the regimen. This method was valuable as it sought to avoid harm to the condition of the patients by only endeavoring to ensure success of the employed treatment. Treatment was commenced in the health facility for about one percent of the patients. In total, 310 out of 7400 patients (about 4%) were left out of the study in the initial stage. This included the patients who developed indicative hypotension, deterioration of the kidney function, and nonconformity. After the stage of active dosage, the patients proceeded to a single blind course of matching placebo for a maximum of 17 days in an effort of establishing the ones whose health situations deteriorated with the withdrawal of the medication and the ones who did not adequately adhere to the regimen. Similarly, in the second phase, about 4% of the patients were ruled out of the study for dissimilar reasons such as deterioration of their conditions and issues of compliance. Sadly, 4 patients passed way in the run-in course for enalapril while in the case of the placebo 34 patients died.
At the close of the period of placebo administration, the patients embarked on either the treatment trial (the ones with overt chronic coronary failure) or prevention trial (those who were seen not to have overt coronary failure). At every follow-up visit, a record was made concerning changes witnessed in the health conditions of the patients, the application of any other drug, any other cases of hospitalization after the initial one, compliance with medication, and witnessed side effects. Though the study made caution at each phase, the use of placebo while being aware that it could be ineffective was wrong as that was tantamount to playing games with the lives of the patients. Instead of using people in the experiment, the investigators should have designed a research with animals such as the guinea pig. If this were the case, perhaps the lives of the 34 patients who passed away in the course of the placebo administration would have been saved.
The investigators used a grouped log-rank statistic (that had 23 centers) in the comparison of the life-table survival charts for the participants randomly assigned for administration of either placebo or enalapril. There was a determination to depend majorly on Lan-DeMets method for statistical directives in the course of temporary analysis and the Kaplan-Meier technique was employed in the creation of life-table plots. The consistency of treatment impacts in the subgroups was gauged by the likelihood ratio test anchored in the Cox regression model. The fact that suitable statistical tests were employed in the study coupled with the adequate data collected boosts the significance of the tests. However, the significance of the dissimilarities that are purportedly the findings of the double blind trial appears to have been overestimated thus weakening the reliability of the research.
Fig. 1: Proportion of occurrences, death or hospitalization, when placebo or enalapril was administered (The Solvd Investigators, 1991, p. 298)
The application of the study could result in a significant decrease in mortality and worsening of the cases of chronic coronary failure due to the incorporation of enalapril in conventional therapy. The influence of enalapril in decreasing mortality and level of hospitalization is statistically significant and medically imperative. The research is credible and the size of the sample representative. Though the study is discussed in a clear way, the application of additional visual aids may enhance the significance of the study particularly by making it easier to understand. The findings from the study have very useful information with insight into the improvement of the quality of care. Nevertheless, there is a need for future research to avoid the weaknesses in this article by such things as including even elderly patients (over 80 years old) and simplifying the terms and findings to make it easy for a layman with no medical expertise to understand the relevance of the study.
Boot, W. R., Simons, D. J., Stothart, C., & Stutts, C. (2013). The pervasive problem with placebos in psychology why active control groups are not sufficient to rule out placebo effects. Perspectives on Psychological Science, 8(4), 445-454.
Hernán, M. A., Hernández-Díaz, S., & Robins, J. M. (2013). Randomized trials analyzed as observational studies. Annals of internal medicine, 159(8), 560-562.
McMurray, J. J., Packer, M., Desai, A. S., Gong, J., Lefkowitz, M. P., Rizkala, A. R., & Zile, M. R. (2014). Angiotensin–neprilysin inhibition versus enalapril in heart failure. New England Journal of Medicine, 371(11), 993-1004.
Muchnik, L., Aral, S., & Taylor, S. J. (2013). Social influence bias: A randomized experiment. Science, 341(6146), 647-651.
Rothman, K. J., Gallacher, J. E., & Hatch, E. E. (2013). Why representativeness should be avoided. International journal of epidemiology, 42(4), 1012-1014.
The Solvd Investigators. (1991). Effect of enalapril on survival in patients with reduced left ventricular ejection fractions and congestive heart failure. The New England Journal of Medicine, 325(5), 293-302.