Objectives and outcomes of a clinical trial

All scientific medical studies are conducted to generate new knowledge about health and disease and to inform clinical practice and public health policies. A medical study is planned based on a hypothesis that justifies the clinical study. The research question arises from a perceived knowledge deficit in a particular subject area. It is antecedent to the research and establishes the study’s direction. A clinical trial aims to find an answer to the main research question or hypothesis that the study plans to answer. Hypothesis testing is the most widely employed method of determining whether clinical study outcomes are positive or negative.

OBJECTIVES OF A STUDY

The objectives of a medical study can be broadly classified into primary and secondary objectives. The study’s hypothesis defines the research’s primary objective and is thus the aim of a medical study. It attempts to find an answer to the main research question or hypothesis. While addressing the primary objectives, additional research questions may also be addressed. These other research questions addressed are called the secondary objectives.[1]

The primary objective of a medical study is typically framed in terms of the study’s endpoint or outcome measure—some examples to explain the same are presented in Table 1.

Table 1.

Examples of objectives of a study

Clinical trial	Primary objective	Secondary objectives
To determine the degree of hypotension of a new drug for induction of anaesthesia	To measure the fall in blood pressure after its administration and compare it with the fall/otherwise after administration of an agent in clinical use	a. Recording other adverse effects of the drug b. Duration of onset of action of the drug c. Interaction with other anaesthetic agents used
To study the antiemetic potential of a new agent	The occurrence of PONV with its use and compare it with the occurrence of PONV with a standard drug/placebo	a. To determine the duration of the effect of the agent b. Sedative effects of the agent c. Adverse effects of the drug
An airway study for an SAD	To determine the seal pressure of the SAD and comparing it with the seal pressure of another SAD	a. To determine the incidence of micro-aspiration with the device used b. Determining the fitting characteristics of SAD in different categories of patients c. Recording the number of attempts needed to insert it d. Assessing the ease of its insertion

PONV=postoperative nausea and vomiting, SAD=supraglottic airway device

Secondary objectives are often included in a medical study to provide additional information about the intervention or exposure under investigation or to explore other research questions of interest. Secondary objectives may consist of assessing the safety and tolerability of the intervention, the effects of the intervention on secondary outcomes (e.g. quality of life, adverse events) or subgroup analyses to identify which patient populations benefit most from the intervention. Samples to explain the same are given in Table 1.

Defining objectives helps ensure that the investigation is designed and powered appropriately to answer the research question(s) of interest, and that the data collected are correctly analysed to answer those questions. The appropriate sample size of the study is based on the incidence/prevalence/any other primary outcome in a similar study conducted earlier or a pilot study. To ensure the statistical value of a study, the design should preferably have only one primary objective.[2]

OUTCOMES

The outcomes of a medical study can be classified into primary and secondary outcomes. The primary outcome of medical research is the main outcome measure that the study aims to answer (i.e. based on the primary objective). In an experimental, semi-experimental or observational research study, the primary study outcome is based on and aligned directly with the primary objective. The secondary outcomes are additional outcome measures that are addressed in the study.

The primary outcome is typically the most important in a study. It is usually chosen to reflect the main research question or hypothesis—some examples to explain the same are presented in Table 2.

Table 2.

Examples of outcomes of a study

Clinical trial	Primary outcome	Secondary outcomes
To determine the degree of hypotension of a new drug for induction of anaesthesia	To determine whether a statistically significant reduction in blood pressure happened with the drug compared to a standard anaesthesia induction agent	a. Recording of rash along the venous path b. Events of cough after its administration
To study the antiemetic potential of a new agent	Whether a statistically significant reduction in the incidence of PONV was seen in the study population vis-a-vis the agent it was compared with	a. Higher incidence of postoperative hypoxaemia b. Hypotension after administration
An airway study for a SAD	Whether the mean airway pressure beyond which the expired tidal volume was statistically lower than the inspired tidal volume and whether it was more/less than the SAD it was compared with	a. Instability of the device in edentulous patients b. Difficulty of insertion in patients with a small lower jaw c. Higher incidence of sore throat in patients receiving it

SAD=supraglottic airway device

Secondary outcomes are often included in a medical study to provide additional information about the intervention or exposure under investigation or to explore other research questions of interest. For example, secondary outcomes might include measurements of safety and tolerability of the intervention, effects on secondary endpoints (e.g. quality of life, adverse events) or subgroup analyses to identify which patient populations benefit most from the intervention. Secondary outcomes logically arise from and directly align with secondary objectives. Samples to explain the same are given in Table 2.

Secondary outcomes may not necessarily be related to the secondary objectives included in the study protocol and may be incidental findings from data analysis. Such secondary outcomes in the study manuscript must be justified. Multiple testing of secondary outcomes increases the family-wise error rate and the probability of at least one false significant result (type I error) among all secondary outcomes studied. Secondary outcomes are helpful if they lend supporting evidence for the primary outcome. Statistically robust secondary outcomes should always be considered and not dismissed based on multiplicity concerns.[3]

A judicious approach should be taken to primary and secondary outcomes and clearly defined. The fewer they are, the better the study.[4] This helps ensure that the investigation is designed and powered appropriately to answer the research question(s) of interest, and that the data collected are analysed correctly to answer those questions. It is also essential to understand that the study may or may not result in the projected outcomes of the hypothesis or may only partially meet or may show significant secondary outcomes.