1993 National Institutes of Health Revitalization Act, which mandated that women and minorities be included in NIH-funded research. The initial large studies on the use of low-dose aspirin to prevent heart attacks that were published in the 1970s and 1980s are often cited as examples of clinical trials that included only men, but from which people drew general conclusions that did not hold true for women. In 1993 the FDA reversed its 1977 guidance, and included in the new guidance a statement that the former restriction was "rigid and paternalistic, leaving virtually no room for the exercise of judgment by responsible research subjects, physician investigators, and investigational review boards (IRBs)". The National Academy of Medicine published a report called "Women and Health Research: Ethical and Legal Issues of Including Women in Clinical Studies" in 1994 and another report in 2001 called "Exploring the Biological Contributions to Human Health: Does Sex Matter?" which each urged including women in clinical trials and running analyses on subpopulations by sex. Although guidelines have been introduced, sex bias remains an issue. A 2001 meta-analysis found that of 120 trials published in the New England Journal of Medicine, on average just 24.6% of participants enrolled were women. In addition, the same 2001 meta-analysis found that 14% of the trials included sex specific data analysis A 2005 review by the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use found that regulation in the US, Europe, and Japan required that clinical trials should reflect the population to whom an intervention will be given, and found that clinical trials that had been submitted to agencies were generally complying with those regulations. A review of NIH-funded studies (not necessarily submitted to regulatory agencies) published between 1995 and 2010 found that they had an "average enrollment of 37% (±6% standard deviation [SD]) women, at an increasing rate over the years. Only 28% of the publications either made some reference to sex/gender-specific results in the text or provided detailed results including sex/gender-specific estimates of effect or tests of interaction." The FDA published a study of the 30 sets of clinical trial data submitted after 2011, and found that for all of them, information by sex was available in public documents, and that almost all of them included sub-analyses by sex. As of 2015, recruiting women to participate in clinical trials remained a challenge. In 2018 the US FDA