Surely you recall ‘Who?’

DON TODD knows his way around the TV business, having spent more than 20 years writing for shows such as “Ugly Betty,” including a few that didn’t work out (“Life as We Know it,” “Inconceivable”). He’s also cheerfully and openly neurotic.

So last year, when ABC picked up his new comedy “Samantha Who?,” starring Christina Applegate as a Chicago advertising exec rebuilding her life after suffering amnesia, Todd was just sure something would happen to screw up his big moment. Like, oh, maybe ... a strike.

“There’s not a therapist in town that will see me anymore,” he joked during an interview at his office on the CBS Radford lot in Studio City. During the writers strike, Todd felt duty-bound to stay away from work, although he could glimpse his assigned studio parking space from the picket lines.

Still unclear, though, is whether the layoff will actually hurt “Samantha Who?,” which returns April 7 with its first new episode in four months. For what it’s worth, the show remains easily the top-rated new comedy in this weird, attenuated season -- CBS’ “The Big Bang Theory” is a distant No. 2. Much of the show’s success last fall had to do with the popularity of its lead-in, “Dancing With the Stars,” as the producers acknowledge. “Samantha Who?” will again enjoy that cushy scheduling spot next month, although of course there are no guarantees when it comes to the TV business these days.

So cast and crew have good reason to hold their breath, waiting to see if audiences troop back the way they did in unexpectedly large numbers last week for CBS’ Monday comedy lineup.

“I absolutely believe it interrupted the momentum,” Applegate told me during a brief chat recently in her dressing room between scenes, referring to the strike. “It was like a blow to the stomach.

“I feel like a new show needs to carry on [without interruption]. People are fickle, audiences are fickle. . . . Leaving it off like that, I think it might be hard for the audience to get back in and remember what was going on. But hopefully we’ll be able to capture them back.”

The presence of “DWTS” is key, as executive producer Peter Traugott acknowledged: “If we had to come back and self-start a time period, that would be a different story. That would definitely make us a lot more nervous. But having that lead-in, I think we feel pretty good about an audience finding the show again.”

The issue has to do with more than just “Samantha Who’s” ability to stand on its own. Industry wisdom dictates that reality shows often don’t mix well on the TV schedule with scripted programs, because the audiences they attract are often very different. But network execs still try; Fox, for example, has tried to jump-start numerous shows by pairing them with “American Idol.”

This approach yielded success with “24” and “House.” But “Idol” has also been yoked to clinkers like “ ‘Til Death,” “Life on a Stick,” “Unan1mous” and more.

So is “Samantha Who?” closer to “House” or “ ‘Til Death?”

The former, the producers hope, naturally. And indeed, although critics were never crazy about the amnesia story line, there’s some evidence viewers feel affection, if not yet “Seinfeld”-esque loyalty, for Applegate and the band of quirky characters that surrounds her, including Jennifer Esposito as Sam’s naughty friend Andrea. The pop-culture site Metacritic.com gave “Samantha Who?” a mediocre 59 (out of 100) rating among TV reviewers, but everyday users scored the comedy at a much stronger 8.5 (out of 10).

Todd argues that if viewers didn’t like the show, they simply wouldn’t watch. “Not every show that aired after ‘Dancing With the Stars’ the last couple of years built an audience,” he said. (True enough: Remember Ted Danson’s ill-fated “Help Me Help You”?)

Back when the producers pitched the show to ABC, “we looked at the network we were making this for, what they had on the network, and where it might work, and consciously planned a show that could go behind any of their hits,” Todd said.

Given that ABC already had a lock on young women with shows like “Desperate Housewives,” “Grey’s Anatomy” and “The Bachelor” -- not to mention “DWTS” -- a sitcom angled toward young women seemed like the safest bet. “They bought the pitch,” Todd said, “because it had an appeal to a demographic they already had.”

Once a show is on the air, that kind of calculation carries it only so far. Applegate is the star, and Todd makes it clear that she’s the centerpiece of the writers’ efforts. Familiar to millions of viewers from her days as the dim-witted teenage daughter on Fox’s “Married ... With Children,” the actress, now 36, also had an ill-fated experience a decade ago on NBC’s sitcom “Jesse.” But she’s retained her appeal among young-adult viewers who now drive ratings.

The key, Todd says, was finding “the right match for tone and material.” Her character’s unusual past on “Samantha Who?” allows her to retain elements of the dumb-blond stereotype while simultaneously portraying a contemporary career woman -- a canny combination.

Further refinements are on the way. Gradually the writers are moving away from the amnesia device that rankled critics and just developing the character relationships.

“At some point, the idea of the amnesia really has to fade away and the idea of a human being learning about themselves and redirecting themselves, that has to be the primary focus,” Applegate said. In one recent episode, “I think there’s one mention of the fact I don’t remember something.”

During the work stoppage, Todd found himself with plenty of time to think about tinkering with the show, even if he couldn’t officially work. He realized that the writers had set too many episodes during winter in Chicago, giving the series a dark, depressing look. So he decided that it would be a magically brief winter on Lake Michigan this year, at least on “Samantha Who?”

He smiled wryly.

“I’ve often said there is an aspirational quality to the show,” he said.

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Contact Scott Collins at scott.collins @latimes.com