The philosophy for OTC study design is significantly different from that of prescription medication studies. With prescription medications, you are typically striving to answer the basic scientific questions of 'can this drug work effectively?' and 'is it safe to administer to people?'. Therefore, it is appropriate to study these new chemical entities primarily in controlled settings with extensive inclusion and exclusion criteria. This provides increased safety for the study participants, who will be using a drug of relatively unknown toxicity, and allows a reduction in the inherent variability of the study population, so as to obtain a clearer scientific answer to the questions of basic safety and efficacy. Every effort is made in studies of this type to control for all possible variables and to reduce random real-world circumstances to a minimum.
In the case of drugs being prepared for the self-medication market, just the opposite sort of philosophy applies. In this situation, a great deal of evidence is already available about the abstract safety and efficacy of the drug. Its basic ability to function has already been well established or it would not have been approved in the first place. The key issue in the switch of drugs is to establish whether the drug can work in the real-world context, with all the inherent happenstance and randomness that implies.
Realism is the key to OTC research design. The best OTC studies are often called 'slice-of-life' studies. This communicates effectively the idea that you want to get a realistic real world impression of what the drug will do when subjected to all the variables of an actual use setting. In order to achieve this, selection criteria should be minimized rather than maximized. You want to study the same kind of population that will come into drug stores and even into supermarkets and actually buy this drug. Eliminating large segments of this population by strict admission criteria will only produce a result that is redundant of what has been previously demonstrated and which is not relevant to the actual conditions of use the drug will encounter. Every effort should be made to simulate the way in which patients will actually use the drug. In some cases, it is even known to go so far as to actually have patients pay for the drug in order to obtain the motivational factors associated with a purchase. This illustrates the degree to which some studies go to ensure that they're actually studying the conditions of use and not some artificial situation which is set up for the study and may give seriously misleading results. In the same philosophical vein, it is important to design the study for minimum interference with the patient. He/She must be left free to act, guided only by the labeling. Excessive intervention by the investigator will distort the results.
Some may react to studies of this type by feeling that they are unscientific. Actually, they are just addressing a different question. What is important to remember is what hypothesis is being tested. At the stage where a drug is being considered for a switch, the question is, 'What impact will this drug have on the public health as it will really be used by the lay public?'. This is the question that the FDA needs answered. Excessively controlled study designs will only detract from the studies' relevance.
These studies are tests of the labeling as much as they are tests of the drug itself. It is essential that the combination of the drug and its OTC labeling work closely together to enable patients to self-medicate effectively. One should never study an OTC drug as the pharmaceutical substance alone, but always as the combination of the labeling and the pharmaceutical. It follows, then, that the development of this labeling is very important for OTC
use. It may, in fact, make the entire difference between a drug being a switch candidate and remaining on prescription status indefinitely. Not only is a great deal of creativity necessary in developing effective labeling but appropriate label comprehension studies are also important in ensuring that the best labeling is obtained.
Research has shown that patients by and large do read labeling and they do heed it, particularly with new drugs that they have not used before. Prior to any program being advanced to the stage of the definitive clinical studies, it is wise to develop a variety of different versions of the proposed labeling, so that these versions can be tested in label comprehension studies. These studies are sometimes organized by the medical department and sometimes they are carried out as market research, since they need not involve actual ingestion of drug. They consist of comparative studies in which patients in a realistic setting read the proposed labeling and then are quizzed on their comprehension of it. In this way, it is possible to see whether they understand how the drug ought to be used and whether they have understood key precautions. It is best to check both short-term and long-term comprehension to see how well the patients are able to remember what they have learned. This sort of pre-screening of labeling can be absolutely essential to success and it has saved many careers by avoiding disasters in large-scale definitive studies.
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