Plaintiff Alan Cler suffered severe injury to his arm and hand after receiving intravenous chemotherapy treatment from defendant Oregon Hematology Oncology Associates, PC. Cler and his wife (plaintiffs) brought this action against defendant, alleging that one of defendant’s nurses had caused Cler’s injury by negligently administering the chemotherapy treatment. During defendant’s closing argument, defense counsel made several factual statements regarding a nurse expert who did not testify at trial; the statements had no basis in this record. The trial court overruled plaintiffs’ counsel’s objections to the statements. The jury returned a verdict for defendant. On appeal, plaintiffs argued that the trial court had abused its discretion in allowing defense counsel, during closing argument, to present facts to the jury regarding the anticipated testimony of an expert witness that was not in the record. The Court of Appeals affirmed the trial court’s decision. Cler v. Providence Health System-Oregon, 222 Or App 183, 192 P3d 838 (2008).1 We allowed plaintiffs’ petition for review and, for the reasons that follow, now reverse and remand for a new trial.
After Cler was diagnosed with Hodgkin’s Lymphoma, a form of cancer, he opted to undergo chemotherapy treatment that included the intravenous injection of a drug called Adriamycin. Adriamycin can cause tissue damage if it leaks out of a patient’s vein and into other tissues. During Cler’s first chemotherapy session, an oncology nurse employed by defendant administered Adriamycin, which leaked from Cler’s vein and caused severe damage to Cler’s arm and hand. Plaintiffs filed this personal injury action, alleging that defendant’s nurse had not met the standard of care required for an oncology nurse in her treatment of Cler. The case proceeded to jury trial.
At the beginning of trial, the parties offered opening statements. During her opening statement, defense counsel told the jury that she would be calling an oncology nurse, a *484nurse manager at Oregon Health Sciences University, to testify as an expert witness. Defense counsel offered a summary of the nurse expert’s expected testimony, namely, that defendant’s nurse had met the applicable standard of care for oncology nurses in administering intravenous chemotherapy treatment and that several other events and circumstances, all consistent with good care, could have resulted in the injury that plaintiff suffered.
On the fifth day of trial, plaintiffs were still presenting their case-in chief. Before plaintiffs called Cler as their last witness, defense counsel stated to the court, “Judge, I do have a doctor here, who I would like to be able to get on if I can.” Plaintiffs’ counsel objected. After an off-the-record discussion in chambers, the judge and the lawyers returned to the courtroom, and the judge addressed the jury: “Jurors, we’re going to give [defense counsel] an opportunity to talk with a couple of her witnesses in the hallway and then we’ll be resuming testimony just shortly.” After a short break, plaintiffs’ counsel called Cler to testify. The next day, defendant’s oncology doctor expert testified. Defense counsel did not call a nurse expert to testify on defendant’s behalf at trial.2
During closing argument, plaintiffs’ counsel drew attention to defendant’s failure to call a nurse expert:
“Can you imagine this institution, Oregon Hematology Oncology, and they have not called an independent nurse expert to justify the care in this case? * * *
“But on a case where we’re talking about nursing care, and everyone agrees * * * when it comes to actually giving the drugs nowadays, this is nursing duty. Nurses do this. Doctors don’t do this. They don’t have an independent nurse expert.
“I mean, can you imagine? Now, there’s a reason. It is probably because they couldn’t get a nurse expert who *485would say that this was okay care. That’s the conclusion that’s easy to draw on.”
Defense counsel raised no objection to those statements. Instead, in her closing argument, defense counsel stated:
“Now, one thing I just want to mention before I forget, [plaintiffs’ counsel] said that we didn’t even call an oncology nurse. And I hope you remember that when I started my case, and I gave my opening statement, I told you that I had [two doctors] and [an oncology nurse] who is the nurse manager at OHSU and has 20 years’ of experience in oncology. I hope you remember that — ”
Plaintiffs’ counsel objected that defense counsel was “close to testifying as opposed to addressing the evidence that was before the court.” The trial court responded: “I’m going to let her continue * * * in the same vein that you addressed the evidence.” Defense counsel continued by stating that, at one point during the trial, her nurse expert had been in the courtroom waiting to testify. After plaintiffs’ counsel objected twice more, the trial court asked counsel to discuss the matter in chambers. Following that discussion, defense counsel continued her closing argument:
“[The oncology nurse expert] was here on [the fifth day of trial,3] prepared to testify in the afternoon. She sat in the courtroom all afternoon, and she didn’t get on because [plaintiffs’ counsel] was calling Mr. Cler in the afternoon. She had to leave on the following day. She got on a plane. She was scheduled to go on vacation. That’s why you didn’t hear from [her]. She was prepared to be here. She sat in the courtroom all that afternoon, and again, she was prepared to testify and would have testified in our case and supported our case.”4
*486In his rebuttal argument, plaintiffs’ counsel addressed defense counsel’s comments concerning the failure of the nurse expert to testify:
“You heard me object to the thing about the nurse expert. I feel pretty strongly about this. Look, anybody that tries these cases knows that you better get your most important and your best witness on.
“Now, you guys sat through the testimony and you know that we accommodated [defense counsel] by taking two witnesses out of turn. She had every, every opportunity to get a nurse expert in to testify in this case. If she didn’t want to call that nurse at some particular time, there’s another procedure that’s available.
“You can take a witness outside the bounds of the courtroom and you can do a videotape deposition and set up a camera and bring it in. You saw — I don’t know if you saw there’s a television in the courtroom for a couple of days. So you can play perpetuated testimony on a TV.
“She had every opportunity under the rules that we do these cases to get this witness in here, and she did not. So I think that you still have to conclude there’s a reason that she did not.”
The trial court gave no special jury instructions regarding the nurse expert, but did give the jury the standard instruction that it must decide the case based on the evidence (testimony and exhibits) presented at trial and that counsel’s opening statements and closing arguments are not evidence. The jury returned a verdict for defendant.
Plaintiffs filed a motion for a new trial, arguing, among other things, that the trial court had abused its discretion by permitting defense counsel to present facts in her closing statement that were not in evidence. The trial court denied plaintiffs’ motion, concluding that the court’s failure to sustain the objections that plaintiffs’ counsel made during defense counsel’s closing argument “did not substantially affect plaintiffs’ rights” because the statements “were not probative of the substantive factual issues in the case, nor did they raise an issue with respect to the credibility of a witness.” The court also noted that plaintiffs’ counsel had been able to rebut defense counsel’s statements in rebuttal “by *487explaining ways in which defendant could have preserved the expert’s testimony for trial and by suggesting that defense counsel made choices regarding the order in which she called her experts.”
Plaintiffs appealed, assigning error to the trial court’s ruling on plaintiffs’ objections to the statements made in defendant’s closing argument. The Court of Appeals agreed with plaintiffs that the trial court had abused its discretion in allowing improper argument by defense counsel during closing statements. Cler, 220 Or App at 189. The court concluded, however, that the error did not substantially affect plaintiffs’ rights for three reasons: (1) the trial court instructed the jury that opening and closing statements are not evidence; (2) the discussion of plaintiffs’ nurse expert “was not even a forkful of the entire evidentiary pie;” and (3) the trial court, which was in the best position to evaluate the effect of the improper argument, assessed any prejudice to plaintiffs as minimal. Id. at 191-92. Accordingly, the Court of Appeals affirmed the trial court judgment.
On review, the parties reprise the arguments that they made to the Court of Appeals. Plaintiffs argue that a trial court abuses its discretion by allowing counsel to deliberately relate facts not in evidence to the jury during argument, and that such action is per se prejudicial because it violates the other party’s “right to a fair trial within well-established rules.” In response, defendant argues that a trial court does not abuse its discretion by allowing counsel to introduce facts not in evidence during argument when those facts are collateral and when the opposing counsel has “opened the door” with his or her own improper argument. Defendant further argues that, on this record, plaintiffs cannot demonstrate that the statements at issue by defense counsel were sufficiently prejudicial so as to warrant reversal.
We review a trial court’s decisions regarding control of jury argument for an abuse of discretion. R.J. Frank Realty, Inc. v. Heuvel, 284 Or 301, 306, 586 P2d 1123 (1978). In general, in presenting closing arguments to the jury, counsel have “a large degree of freedom” to comment on the evidence submitted and urge the jury to draw any and all legitimate inferences from that evidence. Huber v. Miller, 41 Or *488103, 115, 68 P 400 (1902). However, that freedom is not without limitations:5 One such limitation is that counsel may not make “statements of facts outside the range of evidence.” Id.; see also John H. Wigmore, 6 Evidence in Trials at Common Law § 1807 (Chadbourn rev 1979) (“[C]ounsel must not make assertions as to facts of which evidence must have been introduced but has not been or will not be introduced.” (emphasis omitted)); Trial, 88 CJS 353 § 309 (2008) (“Counsel must be confined to the issues and the evidence, and will not be allowed to comment on or state facts not in evidence or within the issues.”).
In closing argument in this case, over plaintiffs’ counsel’s objection, defense counsel made four statements of fact that were not testified to by any witness or otherwise admitted into evidence: (1) an oncology nurse manager with 20 years of experience had been prepared to testify on defendant’s behalf; (2) the nurse expert had been waiting in the courtroom to testify on the afternoon of the fifth day of trial; (3) the reason that the nurse expert did not testify was because plaintiffs’ counsel called a witness that afternoon and the nurse expert had to go on vacation the following day; and (4) if the nurse expert had testified, she would have “supported [defendant’s] case.” Defense counsel had no basis in the record to offer those statements to the jury in her closing argument.
Defendant submits that, in this case, the extra-record statements were proper because, during closing argument, plaintiffs’ counsel had commented on defendant’s failure to call a nurse expert, asking the jury to draw the inference that defendant could not find a nurse expert who would have testified that the nurse who treated Mr. Cler had acted within the applicable standard of care. According to defendant, plaintiffs’ counsel’s comment was improper because plaintiffs’ counsel was aware that the nurse expert had not testified because of scheduling issues. As a result, *489defendant concludes, plaintiffs’ misleading statements “provoked” or “invited” defense counsel’s statements. We disagree.
In calling attention to defendant’s failure to call a nurse expert, plaintiffs’ counsel invoked the missing witness inference. In general terms, that inference provides that, “[w]hen it would be natural under the circumstances for a party to call a particular witness * * * and the party fails to do so, tradition has allowed the adversary to use this failure as the basis for invoking an adverse inference.” 2 McCormick on Evidence § 264, at 220 (6th ed 2006). In Bohle v. Matson Navigation Co., 243 Or 196, 198, 412 P2d 367 (1966), the court approved generally the use of that inference, holding that the plaintiffs counsel in a personal injury case should have been allowed to comment in closing argument on the failure of the defendant to call a doctor who had examined the plaintiff at defendant’s request because “it is a natural inference that he would have been called if his testimony would help the defendant’s case.” Id. The invocation of the missing witness inference by plaintiffs counsel was consistent with the holding in Bohle. As the trial court acknowledged, plaintiffs counsel’s comments “addressed the evidence” in the trial record.
If a party believes that an opponent has invoked the missing witness inference improperly, the party is not without recourse. The party may timely object, and, if necessary, move to strike or request a curative jury instruction. If evidence in the record provides an alternative explanation for a party’s failure to call a witness, that party properly may comment thereon. Trial, 88 CJS 360 § 313 (“It is proper for counsel to account for the absence of a desired witness where such absence would be a proper subject for comment by his or her opponent, where the explanation is based on evidence in the record, but not otherwise.” (emphasis added; footnote omitted)). But a party may not pursue the course of action that defendant chose in this case: A party may not deprive the court of the opportunity to rule on the propriety of an opponent’s statement by remaining silent during the opponent’s closing argument, and then resorting to self-help by presenting argument based on facts not in evidence. Here, defense *490counsel failed to object to plaintiffs’ counsel’s use of the missing witness inference in closing argument. Defense counsel never placed the propriety of plaintiffs’ counsel’s statements at issue at trial and that issue is not properly assigned as error on review.
The Court of Appeals, in assessing whether the trial court abused its discretion, determined that jury argument may refer to matters that are within the scope of the issues and the evidence, but that evidence outside the record may not be suggested by any means. 222 Or App 183. For that proposition, the Court of Appeals cited ORS 40.025(3) (OEC 103(3)), which provides:
“In jury cases, proceedings shall be conducted, to the extent practicable, so as to prevent inadmissible evidence from being suggested to the jury by any means, such as making statements or offers of proof or asking questions in the hearing of the jury.”
We agree with the Court of Appeals. Accordingly, we have no trouble also agreeing with the Court of Appeals that the trial court abused its discretion by overruling plaintiffs’ objections to defendant’s improper argument.
Having concluded that the trial court abused its discretion in allowing defense counsel’s statements, we turn to the question of whether that error requires reversal. We will reverse a trial court’s judgment only if the trial court’s error substantially affected a party’s rights. See ORS 19.415(2) (“No judgment shall be reversed or modified except for error substantially affecting the rights of a party.”).
In addressing plaintiffs’ contention that defense counsel’s statements regarding facts not in evidence substantially affected plaintiffs’ rights, we focus first on the particular right at issue in this case: the right to require opposing counsel to confine her closing argument to the jury to facts admitted into evidence and permissible inferences from those facts. Although not evidence themselves, closing arguments “are an integral part of trial” that can alter the result of the trial:
“They provide the attorneys with their final opportunity to ‘persuade the jury to adopt a particular view of the facts.’ *491Ireland v. Mitchell, 226 Or 286, 295, 359 P2d 894 (1961). It is through closing arguments that the attorneys are able to fully frame the issues and remind the jury of evidence that they may have heard days earlier. Further, arguments give the attorneys a chance to explain the evidence in narrative form. That narrative function of arguments — the opportunity to tell the story of the case — is essential to effective advocacy, and the ability to do so can alter the jury’s understanding of the evidence and ultimately change the outcome of a given case.”
Charles v. Palomo, 347 Or 695, 705, 227 P3d 737 (2010) (holding that the trial court’s error in denying the plaintiff rebuttal argument substantially affected the plaintiffs rights). The integrity of closing arguments can only be ensured when the court requires the parties to limit their arguments to the facts in evidence and permissible inferences from those facts. See Kuehl v. Hamilton, 136 Or 240, 249, 297 P 1043 (1931) (noting that “[e]very litigant is entitled to a fair trial, and this result cannot be achieved if counsel is permitted to make statements to the jury of facts not testified to by any witness nor admissible in evidence”). Thus, a party’s introduction of facts not in evidence during closing arguments can substantially affect the opposing party’s rights.
We determine that, in this case, defense counsel’s introduction during closing argument of facts not in evidence substantially affected plaintiffs’ rights. In his closing argument, plaintiffs’ counsel framed his narrative of the case. One aspect of that narrative involved asking the jury to draw an inference from defendant’s failure to call a nurse expert.6 Defense counsel then framed a different narrative of the case, but in doing so, impermissibly interjected extra-record facts into the case after the parties had rested. Defense counsel introduced those facts over plaintiffs’ counsel’s repeated objections and after an in-chambers discussion between the court and counsel. In that context, from the jury’s perspective, defendant’s account of the absence of the nurse expert would appear to have received the trial court’s imprimatur. *492Thus, plaintiffs’ counsel’s ability to rebut defense counsel’s explanation of the nurse expert’s absence was weakened substantially.
Moreover, by making the assertion that the nurse expert “would have supported” defendant’s case, defense counsel supplied, at least in general terms, the testimony of a witness who was not subject to oath or cross-examination.7 See ORS 40.320(1) (“Before testifying, every witness shall be required to declare that the witness will testify truthfully, by oath or affirmation * * *.); Wigmore, 6 Evidence in Trials at Common Law § 1806 (when counsel argues facts not in evidence, counsel becomes a witness without being subject to cross-examination, in violation of the fundamental purpose of the hearsay rule). The trial court’s admonition to the jury that the lawyers’ arguments “are not evidence” does not overcome that problem, in our view. That admonition operates on the assumption, noted above, that the record evidence frames the context within which lawyer argumentation permissibly may occur. The court’s admonition helps the jury understand that it must not confuse a lawyer’s advocacy about the record with the actual witness testimony and other evidence that the court has admitted into the record in accordance with the rules of evidence. The comments of defense counsel to the jury here, however, did not simply convey her view of the record evidence. Rather, defense counsel characterized for the jury the purported testimony of a witness who never took the *493witness stand. That conduct creates an unacceptable risk that the jury would consider the statement as that of the unsworn witness and not solely that of the lawyer. ORS 40.025(3) deters the suggestion of inadmissible evidence to the jury by any means, including through counsel’s statements; it does not somehow authorize that sort of conduct so long as the trial court admonishes the jury that the statements are not evidence. For that reason, the court’s admonition to the jury does not eliminate the prejudicial effect of the trial court’s error.
The assertion that a nurse expert would have supported defendant’s position was material to the central issue in the case: whether defendant’s nurse complied with the applicable standard of care for oncology nurses. Because defense counsel’s assertion that the nurse expert “would have supported” defendant’s case was not based on evidence in the record, the court’s ruling deprived plaintiffs’ counsel of the opportunity to cross-examine that factual assertion or otherwise rebut defense counsel’s factual claim. In light of those circumstances, we conclude that the trial court’s failure to sustain plaintiffs’ objections to defense counsel’s comments substantially affected plaintiffs’ rights. ORS 19.415(2).
The decision of the Court of Appeals is reversed. The judgment of the circuit court is reversed, and the case is remanded to the circuit court for further proceedings.
Providence Health System-Oregon was dismissed from the action and is not a party to this appeal. All references to “defendant” are to Oregon Hematology Oncology Associates, PC.
The parties dispute the details of what occurred during the in-chambers discussion with the judge, as well as the details of the scheduling issues. In our view, the details surrounding the nurse’s failure to testify are not pertinent to the question before us on review. The pertinent fact is that defendant did not ultimately call the oncology nurse expert to testify.
Although defense counsel actually referred to the sixth day of trial, her reference to Mr. Cler and the surrounding context make it clear that she meant the fifth day of trial.
Although plaintiffs did not object again at this point, we determine that plaintiffs’ earlier objections adequately preserved plaintiffs’ argument that defense counsel was impermissibly arguing facts not in evidence. As the trial court later observed in its order denying plaintiffs’ motion for a new trial, “after the in-chambers discussion between the [trial court] and counsel, plaintiffs’ counsel may have felt it would be futile to continue with his same objections.”
See, e.g.,R.J. Frank Realty, 284 Or at 306 (counsel should refrain from abusive arguments); State Highway Comm’n v. Callahan, 242 Or 551, 558, 410 P2d 818 (1966) (arguments that are “highly inflammatory * * * and had no reasonable relevance” to the issues in the case are improper); Bratt v. Smith, 180 Or 50, 60, 175 P2d 444 (1946) (arguments that directly appeal to “passion and prejudice” are beyond the bounds of legitimate comment on the evidence).
The dissent asserts that we have treated plaintiffs’ jury argument as irrelevant to the analysis of prejudice. We disagree. We have considered the entire record, including plaintiff’s jury argument, to determine whether the trial court’s error “substantially affect[ed] the rights of a party.” ORS 19.415(2).
The dissent has determined that plaintiffs’ argument to the jury was not proper and amounted to a misrepresentation. From that premise, the dissent argues that defense counsel sought only to correct that misrepresentation by referring to facts that, according to the dissent, the jury likely already knew by, for example, viewing people sitting in the courtroom during trial and speculating about how they might testify if called. We decline to consider those assertions as facts established in the record. Although the dissent cites several legal propositions with which we have no disagreement, we read the factual record quite differently; our different reading of the record supports our disposition here. For example, in our view, plaintiffs’ counsel’s closing argument was not a misrepresentation and was not improper. That is so because, according to the record, the defense had not called a nurse expert witness, either in person or by introducing an expert’s testimony through a deposition. Nothing compelled plaintiffs’ counsel to concur with defense counsel’s asserted reason for not calling the expert witness or the claim that the witness would have supported defendant’s case. The dissent apparently believes that defense counsel conveyed nothing of the actual substance of the nurse expert’s testimony to the jury but, again, we read the record differently and reach a different conclusion.