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Dosing and Intervention
Chapter 10
Dosing and Intervention
10.1 BACKGROUND
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10.1.1 Definition of Intervention Most clinical studies involve an intervention, that is a drug, a medical device, a technique (e.g., psychotherapy, an exercise, a muscle or spinal manipulation), or a behavior modification (e.g., change in diet or habits) designed to affect a clinical phenomenon. The goal of many clinical studies is to assess the effectiveness and safety of an intervention. This intervention can be: ●
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invasive (i.e., an intervention, such as an angioplasty stent or a needle, that somehow enters or penetrates the body) or noninvasive (i.e., an intervention such as psychotherapy, a bandage, a heating device, or a compression device that does not enter or penetrate the body); preventive (i.e., prevents the occurrence of an event, such as a vaccine) or therapeutic (i.e., treats symptoms or a disease, such as a drug); acute (i.e., administered over a short period of time) or chronic (i.e., administered regularly over a long period of time).
Not all interventions are amenable to clinical studies. For an intervention to be adequately studied in a clinical study, the intervention must be: ●
Reproducible: For results of clinical study to be generalizable, the intervention must be reproducible, that is, practicing clinicians should be able to perform the intervention in the same manner in real-world settings. An intervention that can be performed by only one person in the world, requires very scarce resources or environments (e.g., a ritual that requires a solar eclipse), or lacks clearly defined protocols and instructions (e.g., magical healers that cannot explain their techniques) is not reproducible.
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Standardized: Standardization is essential. Different batches of the same drug should have equivalent quantities of active ingredients, bioavailability, and routes of administration. A medical device should have the same specifications (e.g., size, weight, and materials) and be built, assembled, and placed in or on patients in the same manner. Standardization is especially important with nondrug interventions such as surgery or behavioral techniques. Performing the intervention differently each time (e.g., using different techniques, doses, or timing) will make it impossible to draw any consistent conclusions about the intervention. Clearly defined: Know and define what the intervention is and when it begins and ends. Minimize the number of interventions occurring at one time so that you can establish which intervention is having the effect. You cannot adequately characterize the effects of an intervention until you know how long the intervention took place and when the intervention was completed. For acute and short-term interventions, the start and stop times may be easy to define. For chronic interventions, you may have to arbitrarily set start and stop times.
In addition, you must know the intervention’s operator dependency. Any intervention must be administered. Intervention administration ranges from the simple and straightforward (e.g., giving a patient a pill to swallow) to the complex and difficult (e.g., surgical procedure). Understand how much the operator (i.e., the person or persons administering the intervention) affects the characteristics and impact of the intervention. For example, surgical procedures are highly operator dependent (i.e., a skilled surgeon will perform the intervention much more effectively than an unskilled surgeon), but giving a patient an oral medication is not very operator dependent (i.e., most people can put a pill in a patient’s mouth). If an intervention is highly operator dependent, then 181
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Dosing and Intervention
10.1 BACKGROUND
●
10.1.1 Definition of Intervention Most clinical studies involve an intervention, that is a drug, a medical device, a technique (e.g., psychotherapy, an exercise, a muscle or spinal manipulation), or a behavior modification (e.g., change in diet or habits) designed to affect a clinical phenomenon. The goal of many clinical studies is to assess the effectiveness and safety of an intervention. This intervention can be: ●
●
●
invasive (i.e., an intervention, such as an angioplasty stent or a needle, that somehow enters or penetrates the body) or noninvasive (i.e., an intervention such as psychotherapy, a bandage, a heating device, or a compression device that does not enter or penetrate the body); preventive (i.e., prevents the occurrence of an event, such as a vaccine) or therapeutic (i.e., treats symptoms or a disease, such as a drug); acute (i.e., administered over a short period of time) or chronic (i.e., administered regularly over a long period of time).
Not all interventions are amenable to clinical studies. For an intervention to be adequately studied in a clinical study, the intervention must be: ●
Reproducible: For results of clinical study to be generalizable, the intervention must be reproducible, that is, practicing clinicians should be able to perform the intervention in the same manner in real-world settings. An intervention that can be performed by only one person in the world, requires very scarce resources or environments (e.g., a ritual that requires a solar eclipse), or lacks clearly defined protocols and instructions (e.g., magical healers that cannot explain their techniques) is not reproducible.
●
Standardized: Standardization is essential. Different batches of the same drug should have equivalent quantities of active ingredients, bioavailability, and routes of administration. A medical device should have the same specifications (e.g., size, weight, and materials) and be built, assembled, and placed in or on patients in the same manner. Standardization is especially important with nondrug interventions such as surgery or behavioral techniques. Performing the intervention differently each time (e.g., using different techniques, doses, or timing) will make it impossible to draw any consistent conclusions about the intervention. Clearly defined: Know and define what the intervention is and when it begins and ends. Minimize the number of interventions occurring at one time so that you can establish which intervention is having the effect. You cannot adequately characterize the effects of an intervention until you know how long the intervention took place and when the intervention was completed. For acute and short-term interventions, the start and stop times may be easy to define. For chronic interventions, you may have to arbitrarily set start and stop times.
In addition, you must know the intervention’s operator dependency. Any intervention must be administered. Intervention administration ranges from the simple and straightforward (e.g., giving a patient a pill to swallow) to the complex and difficult (e.g., surgical procedure). Understand how much the operator (i.e., the person or persons administering the intervention) affects the characteristics and impact of the intervention. For example, surgical procedures are highly operator dependent (i.e., a skilled surgeon will perform the intervention much more effectively than an unskilled surgeon), but giving a patient an oral medication is not very operator dependent (i.e., most people can put a pill in a patient’s mouth). If an intervention is highly operator dependent, then 181
Ch010-P373695.indd 181
5/24/200