The FDA required that Celgene Corporation, which planned to market thalidomide under the brand name Thalomid, establish a system for thalidomide education and prescribing safety (STEPS) oversight program. The conditions required under the program include limiting prescription and dispensing rights to authorized prescribers and pharmacies only, keeping a registry of all patients prescribed thalidomide, providing extensive patient education about the risks associated with the drug, and providing periodic pregnancy tests for women who take the drug.[47]In 2010, the World Health Organization (WHO) stated that it did not recommend thalidomide for leprosy due to the difficulty of adequately controlling its use, and due to the availability of clofazimine.[48]Shortly after the teratogenic properties of thalidomide were recognized in the mid-1960s, its anti-cancer potential was explored and two clinical trials were conducted in people with advanced cancer, including some people with multiple myeloma; the trials were inconclusive.[49]Little further work was done with thalidomide in cancer until the 1990s.[49]Judah Folkman pioneered studies into the role of angiogenesis (the proliferation and growth of blood vessels) in the development of cancer, and in the early 1970s had shown that solid tumors could not expand without it.[50][51] In 1993 he surprised the scientific world by hypothesizing the same was true of blood cancers,[52] and the next year he published work showing that a biomarker of angiogenesis was higher in all people with cancer, but especially high in people with blood cancers, and other evidence emerged as well.[53] Meanwhile, a member of his lab, Robert D'Amato, who was looking for angiogenesis inhibitors, discovered in 1994 that thalidomide inhibited angiogenesis[54] and was effective in suppressing tumor growth in rabbits.[55] Around that time, the wife of a man who was dying of multiple myeloma and whom standard treatments had failed, called Folkman asking him about his anti-angiogenesis ideas.[51] Folkman persuaded the patient's doctor to try thalidomide, and that doctor conducted a clinical trial of thalidomide for people with multiple myeloma in which about a third of the subjects responded to the treatment.[51] The results of that trial were published in the New England Journal of Medicine in 1999.[51][56]After further work was done by Celgene and others, in 2006 the U.S. Food and Drug Administration granted accelerated approval for thalidomide in combination with dexamethasone for the treatment of newly diagnosed multiple myeloma patients.[51][57]It was also evaluated whether thalidomide can be combined with melphalan and prednisone for patients with multiple myeloma. This combination of drugs probably results in an increase of the overall survival.[58]Baby born to a mother who had taken thalidomide while pregnantIn the late 1950s and early 1960s, more than 10,000 children in 46 countries were born with deformities, such as phocomelia, as a consequence of thalidomide use.[59] The severity and location of the deformities depended on how many days into the pregnancy the mother was before beginning treatment; thalidomide taken on the 20th day of pregnancy caused central brain damage, day 21 would damage the eyes, day 22 the ears and face, day 24 the arms, and leg damage would occur if taken up to day 28. Thalidomide did not damage the fetus if taken after 42 days gestation.[37]It is not known exactly how many worldwide victims of the drug there have been, although estimates range from 10,000 to 20,000.[60] Despite the side effects, thalidomide was sold in pharmacies in Canada until 1962.[41][61]The disaster prompted many countries to introduce tougher rules for the testing and licensing of drugs, such as the Kefauver Harris Amendment[68] (U.S.), Directive 65/65/EEC1 (E.U.),[69] and the Medicines Act 1968 (UK).[70][71] In the United States, the new regulations strengthened the FDA, among other ways, by requiring applicants to prove efficacy and to disclose all side effects encountered in testing.