OR WAIT 15 SECS
What to consider if the clinical trial substantiating your U.S. advertising claim is conducted in a foreign country.
Under FTC standards, advertising claims promoting a health benefit must be truthful, non-misleading, and supported by “competent and reliable scientific evidence.”(1) In some instances, the only adequate evidence will be a clinical trial. However, whether or not the FTC will accept clinical trials conducted outside of the United States as adequate substantiation has become a far more important question in recent years.
In the last couple of years, the FTC has been clearer than ever before that it expects advertisers making strong cause-and-effect claims (e.g., “Helps you build muscle,” “Lose weight,” “Helps prevent irregularity”) to possess, at a minimum, at least one well-designed and reliable clinical study. Yet, at the same time, FTC staff-those who conduct FTC investigations-have made statements that suggest a growing skepticism of clinical trials conducted abroad. Thus, companies seeking to make cause-and-effect claims are left to wonder what risk they take if they either conduct testing abroad or rely on an existing trial that was conducted overseas.
This article will, 1) review the FTC’s increased emphasis on clinical trials for certain types of health-benefit claims, 2) discuss where the Commission currently stands on advertisers using clinical trials conducted abroad as substantiation, and 3) provide some practical pointers on minimizing risk, whether a company plans to commission a trial in a foreign country or seeks to rely on a foreign clinical study that is already in existence.
In the past two years, the FTC has taken a hard look at the substantiation behind advertising claims for all sorts of products that promote health benefits. It has investigated products such as “toning” sneakers, dietary supplements, “at home” genetic testing kits, homeopathic products, sports drinks, probiotic yogurt, and even a SmartPhone application that was promoted for health benefits. The Commission has indicated, through its orders against advertisers, that many cause-and-effect claims will require some sort of well-designed human studies.
At least five orders issued in the last two years require the named parties to possess “at least two adequate and well-controlled human studies” for any future weight-loss claims.(2) Two orders have addressed future claims that certain foods, including yogurts and dairy drinks, will help treat gastrointestinal ailments, including occasional irregularity.(3) Those orders also require the named parties to possess “at least two adequate and well-controlled human studies.”(4) Two orders against the makers of a purported skin-clearing SmartPhone application require “at least two adequate and well-controlled human studies” for any future claims that an app can help treat acne.(5) Finally, an order against a leading maker of toning shoes requires “at least one adequate and well-controlled human study” for future claims that any footwear or apparel “is effective in strengthening muscles.”(6)
Although the recent settlement orders on cause-and-effect claims technically apply only to the named parties, statements by FTC staff have made clear that any advertiser contemplating making similar claims should consider the new settlement orders. For instance, David Vladeck, Director of the FTC’s Bureau of Consumer Protection, has emphasized in speeches that the orders represent the application of current guidance and “settled law” to certain types of health-benefit claims.(7)
FTC guidance speaks to the use of foreign trials only briefly, and in broad terms. Guidance on the competent and reliable standard states that the FTC will accept a clinical study conducted in a foreign country “as long as the design and implementation of the study are scientifically sound.”(9) The guidance also notes briefly, and logically, that “[a]ny foreign research submitted [in a foreign language] to the FTC in the course of an investigation should be presented in English translation and with sufficient detail to allow the agency to evaluate the study.”(10)
The FTC’s guidance might lead an advertiser to believe that a foreign trial will be viewed in the same light as any other trial. But recent statements by FTC staff suggest otherwise.
At the same time that the FTC has scrutinized the science behind health-benefit claims more closely, statements by agency staff have indicated growing skepticism toward foreign research. In June 2011, a trade group hosted a webinar on substantiating dietary supplement claims. Richard Cleland, who is an assistant director of the FTC’s advertising division, discussed the use of foreign clinical trials.(11) He stated that although the FTC will accept any scientific evidence that meets the competent and reliable standard, many trials conducted in foreign countries “don’t seem to necessarily have the same rigorous standards as the research that’s conducted in the U.S.”(12) He stated, in no uncertain terms, that “when [staff] starts looking at the underlying data [from foreign studies], we find a whole lot of garbage.”(13)
Against this background-with little specific guidance on the part of regulators-if an advertiser seeks to conduct or rely on a foreign study, it obviously must do so very carefully. Practically speaking, studies conducted abroad likely need to meet not only the usual standard for competent and reliable research but also have some other, added indicia of reliability to overcome doubts on the part of regulators.
Details related to the design and conduct of a clinical trial will, of course, vary greatly and depend largely on the particular product and claims. Nevertheless, we have compiled a few pointers that should help any advertiser that seeks to commission a clinical trial abroad. Most of the pointers are aimed at documenting those details about the design and trial conduct that indicate reliability.
Consult with at least one U.S.-based scientific expert and at least one U.S. legal expert. Before designing a protocol or even researching possible locations or institutions, consulting at least one scientific expert and at least one legal expert, who are both stateside, will be helpful. The competent and reliable standard meets at a nexus of science and law. These individuals should be able to help drive the process from designing a protocol to finalizing the study report to meet the competent and reliable standard.
Under the FTC framework, regardless of what type of scientific evidence an advertiser uses as substantiation, that evidence must be 1) “internally valid,” 2) consistent with the totality of available research in the area, and 3) relevant to the product and claims at issue.(14) The lawyer will need to be able to explain what these requirements mean to all involved. The scientific expert should have experience conducting clinical trials on the type of product the advertiser is selling (e.g., a food) and/or the specific benefit or type of benefit the advertiser is seeking to promote (e.g., weight loss). The scientist will need to be knowledgeable enough in the field to be able to speak to the norms of U.S. clinical testing and the body of science in the relevant area.
Importantly, in the context of a foreign trial, the legal and scientific experts will need to be able to assess any potential confounders, like the diet, lifestyle, or characteristics of a certain population that might make the study results less applicable to a U.S. target audience. For instance, a study of a certain food ingredient might not be relevant to an American target audience if the study is conducted in a rural part of a developing country where the diet and lifestyle are drastically different from that of most Americans. The scientist and lawyer will need to be on the lookout for this kind of issue on the front end, as the study protocol is designed and a research institution is selected.
Vet institutions and researchers carefully. The advertiser will need to defend the institution, the population from which it draws study participants, and the researchers who will conduct the trial. To this end, the advertiser should vet the potential institutions, ask for references, ask for examples of any published research from the institution, and obtain the resume of each person who might be involved in the research. From the technicians to the lead researcher, each person who will conduct the trial should be well-qualified, not just to the standards of the foreign country but to the prevailing standards in the United States.
If persons conducting the research obtained U.S. degrees (e.g., a PhD from Cornell University) or have served on U.S. regulatory panels or committees (e.g., National Institutes of Health committees), that may be helpful in bolstering the person’s credentials with an audience of U.S. regulators. The lead researcher should obviously be able to communicate effectively with the advertiser and any scientific and legal experts who are used. Even if someone other than the lead researcher acts as the primary point of contact, being able to ask the lead researcher questions directly will be helpful, if not essential, as the study is planned, conducted, and made into a final study report.
Obtain IRB approval. Institutional Review Board approval is routine for trials conducted in the United States, as well as in many foreign countries. IRB approval relates only to the ethics of a protocol and does not speak directly to scientific soundness. Still, having an IRB approval is one more indicator that, in general, a trial was above-board and conducted according to prevailing U.S. norms.
Keep good records; know what documents are final. A few documents will be essential to showing regulators that a trial is reliable. Those documents include the protocol, the individual data from the trial, and the final written report. Drafts of these documents will doubtless be exchanged. Even the data will be subject to checks against any handwritten forms that were used. When all is said and done, the advertiser will need to have at its fingertips each key document, in final form. Marking all drafts as “DRAFTS” may be helpful. Setting dates for final versions to be completed may also be helpful.
Make sure that researchers double-check every number that is written down and/or entered into the database for the study. In the worst-case scenario, errors in memorializing data can compromise the accuracy of the results of the study. However, even minor, occasional typos or transcription errors that do not affect the results can cast doubt on the reliability of the data when a regulator reviews it later.
Obtain and vet the underlying individual data. FTC guidance makes clear that clinical studies must yield statistically significant results in order to be considered reliable.(15) Making sure that the statistics are correct is especially important for foreign trials. As noted above, FTC staff has stated that data they have reviewed from foreign trials have appeared less reliable than data from U.S. trials.(16)
Make sure that the study report will be well-written. Even if the advertiser is not planning to publish the study, a full written report is essential to be able to show regulators that the conduct of the trial was appropriate and that the results are reliable. After discussing, in general terms, what constitutes valid research, FTC guidance states that “[t]he nature and quality of the written report of the research are also important” and that “[r]esearch cannot be evaluated accurately on the basis of an abstract or an informal summary.”(17) If a study report does not use good, idiomatic English and appropriate scientific language, that can risk raising undue suspicion about researchers’ qualifications.
Double-check every number in the report. Just like in the data, typos or errors in the written report can cast doubt on the study. Drafts of the report should be reviewed carefully. Every number listed-from the age of participants to the final results-should be double-checked against the data by at least two different people.
Consider publishing the trial in a U.S. or foreign journal. Publishing can be another means of bolstering the credibility of a trial that was conducted abroad. In fact, FTC guidance states as follows:
[A]lthough the FTC does not require that studies be published and will consider unpublished, proprietary research, the publication of a peer-reviewed study in a reputable journal indicates that the research has received some measure of scrutiny. At the same time, advertisers should not rely simply on the fact that research is published as proof of the efficacy of a supplement. Research may yield results that are of sufficient interest to the scientific community to warrant publication, but publication does not necessarily mean that such research is conclusive evidence of a substance’s effect.(18)
For a company seeking to rely on a foreign trial that is already in existence, relevance and reliability are the two main considerations. The company will need to consider, first and foremost, whether the study participants were similar to the U.S. target audience in terms of diet, lifestyle, and physical characteristics, and whether the product that was tested is comparable to the company’s product. Any significant discrepancies will undercut the usefulness of the study.
Also, keep in mind that an existing study may not provide detailed information either on participants or the product tested. If little information is given, the study may be of little substantiation value unless the researchers can be contacted and can provide additional information and documentation.
In order to ensure that the study is reliable, the advertiser should assess the quality of the study report; the quality of the journal, if the study was published; and the qualifications of the researchers. If the underlying data from the trial is available, the advertiser should vet the data. If a study has many indices of a reliable and relevant trial, but was unpublished or published in a little-known journal, having a U.S. expert provide a report on the trial can be helpful. Ideally, an expert report will highlight the strengths of the study and place it in the context of similar U.S. research.