For example if we look at proteins, the basic molecular machines of life. The average protein has a specificity of 10exp480 out of all the different protein possibilities about 10exp5 of them are used in life, and this does not include denatured forms. Frankly, there is not enough material or time in the universe to make it even remotely possible for a single protein to be created by random chance. Luckily all the information to produce a protein is carried in the DNA and a protein can be created by those instructions within a living cell. Of course, you can see the problem right there. Where did the living cell come from. Since there is not enough material or time, we may conclude that the information necessary came from outside of space time. How ones deals with information that comes from outside our perceivable 4 dimensional existence is up to the individual, and far exceeds the scope of the field of biology.
Creation of a protein has nothing to do with "macro change." And evolution explicitly denies that biomolecules came about through "random chance" but says that at every stage those with a survival advantage were favored over others.