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Despite his high critical standing, Clayton encountered repeated career setbacks after the release of Our Mother's House and over the decade and a half between the release of Our Mother's House (1967) and Something Wicked This Way Comes (1983), he was only able to complete one feature as a director, The Great Gatsby (1974). One reason was Clayton's own perfectionism as a filmmaker; he was known for his discernment and taste, his painstaking and meticulous approach to his work, and his desire not to repeat himself, and in his biographer's words, Clayton "never made a film he did not want to make". Consequently, he rejected many notable films in the wake of Room at the Top. In 1969, despite his love of the book, he turned down the chance to direct They Shoot Horses, Don't They? because he did not want to take over a film that had already been prepared and cast, and was ready to shoot – although his decision opened up a career-making opportunity for his replacement, Sydney Pollack. Later still, in 1977, he turned down the chance to direct the film that was eventually made as Alien by Ridley Scott.
Clayton's output was also compromised by the inherent riskiness of the film business. As his biographer Neil Sinyard elucidates, Clayton worked intensively on many projects throughout his directing career, but for various reasons most never came to fruition. Among the projects that Clayton was never able to bring to the screen, or which were eventually made by other directors, were:
Another complicating factor in Clayton's career was that several film projects were cancelled without warning when pre-production was well advanced – in one case, just two weeks before shooting was to have started. Neil Sinyard nominates three major projects, Casualties of War, Fall Creek, and Silence, the successive failures of which reportedly devastated Clayton, and Clayton himself later opined that these setbacks contributed to his subsequent health problems:
In 1977, as compensation for the cancellation of Silence, Fox offered Clayton the chance to film a new science fiction script co-credited to David Giler and Dan O'Bannon, but Clayton turned down the film (Alien), and it was ultimately given to Ridley Scott who, like Sydney Pollack before him, scored a career-making hit. A few months later, Clayton suffered a major stroke which robbed him of the ability to speak. He was helped to recover by his wife Haya, and a group of close friends, but he later revealed that he deliberately kept his condition secret because he feared he might not get work again if his affliction became known. He did not commit to another assignment for five years.