# Questions From Users of the Manual

Q: Should “least squares mean” be hyphenated? Can the acronym LSM be used or is LS preferred?

A: In the glossary in the statistics chapter, you’ll see that there is no hyphen used in “least squares method,” so I would extrapolate from that to say no hyphen is required in “least squares mean.” If this term comes up so frequently in the manuscript that you feel an abbreviation is warranted, we indicate no preference for what that abbreviation is. Just be sure it’s used consistently throughout.—Cheryl Iverson, MA

# Quiz Yourself

Number needed to treat (NNT) is the number of patients who must be treated with an intervention for a specific period to prevent 1 bad outcome or result in 1 good outcome. What is the reciprocal of the NNT? Use your mouse to highlight the answer:

Absolute risk reduction, which is the proportion in the control group experiencing an event minus the proportion in the intervention group experiencing an event, is the reciprocal of the NNT.

See §20.9 for a Glossary of Statistical Terms.—Laura King, MA, MFA, ELS

# Putting P Values in Their Place

Although I am not a statistician, I find something very appealing about mathematics and statistics and am pleased when I find a source to help me understand some of the concepts involved. One of these sources intersects with my obsession with politics: Nate Silver’s website fivethirtyeight.com. Yesterday, during a scan of fivethirtyeight’s recent posts, this one by Christie Ashwanden caught my eye: “Statisticians Found One Thing They Can Agree On: It’s Time to Stop Misusing P-Values.”

P values and data in general are frequently on the minds of manuscript editors at the JAMA Network. Instead of just making sure that statistical significance is defined and P values provided, we always ask for odds ratios or 95% confidence intervals to go with them. P values are just not enough anymore, and Ashwanden’s article was really useful in helping me understand why these additional data are needed (as well as making me feel better about not fully understanding the definition of a P value—it turns out I’m not alone. According to another fivethirtyeight article, “Not Even Scientists Can Easily Explain P-Values”). One of the bad things about relying on P values alone is that they are used as a “litmus test” for publication. Findings with low P values but not contextual data are published, yet important studies with high P values are not—and this has real scientific and medical consequences. These articles explain why P values only can  be a cause for concern.

And then there was even more information about statistical significance to think about. A colleague shared a link to a story on vox.com by Julia Belluz: “An Unhealthy Obsession With P-Values Is Ruining Science.” This article a discussed a recent report in JAMA  by Chavalarias et al “that should make any nerd think twice about p-values.” The recent “epidemic” of statistical significance means that “as p-values have become more popular, they’ve also become more meaningless.” Belluz also provides a useful example of what a P value will and will not tell researchers in, say, a drug study, and wraps up with highlights of the American Statistical Association’s guide to using P values.—Karen Boyd

# Quiz Yourself

Do you know the difference between the terms multivariable and multivariate? One term refers to multiple predictors (independent variables) for a single outcome (dependent variable), and the other term refers to 1 or more independent variables for multiple outcomes? Which is which?

Multivariable refers to multiple predictors (independent variables) for a single outcome (dependent variable). Multivariate refers to 1 or more independent variables for multiple outcomes. Therefore, analyses can be described as multivariable, to indicate the number of predictors, or as multivariate, to indicate the type of outcome.—Laura King, ELS

# Lies and Statistics

Check out this post from Skeptical Scalpel about uncool tricks with statistical graphs. Editors beware!—Brenda Gregoline, ELS

# Questions From Users of the Manual

Q: If there is a column for P values in a table and if a P value “straddles” rows (eg, provides the P value for men vs women), how should this be shown?

A: There are several options, with option 1 being preferred:

1. Center the P value between the items it compares (eg, between the values for men and women) and consider the use of a side brace.

2. If only 2 items are being compared, list the P value on the line giving the overall category (eg, Sex).

3. Use footnotes to indicate the P value for items being compared (eg, use a superscript “a” next to the value for men and the value for women and indicate the P value for this comparison in a footnote labeled “a”).

Q: If some of the confidence intervals given in a table column include negative values, how do you combine the minus sign and the hyphen that would normally be used in such a range in a table?

A: With ranges that include a minus sign, use to to express the range, rather than a hyphen. Carry this style throughout the entire table, even for those values that do not include a minus sign.—Cheryl Iverson, MA

# Significant and Significance

If there is any doubt about whether significant/significance refers to statistical significance, clinical significance, or simply something “important” or “noteworthy,” choose another word or include a modifier that removes any ambiguity for the reader.

The AMA Manual of Style (§20.9, Glossary of Statistical Terms, pp 893-894 in print) includes definitions for statistical significance (the testing of the null hypothesis of no difference between groups; a significant result rejects the null hypothesis) and clinical significance (involves a judgment as to whether the risk factor or intervention studied would affect a patient’s outcome enough to make a difference for the patient; may be used interchangeably with clinical importance). Significant and significance also are used in more general contexts to describe worthiness or importance.

Often the context in which the word appears will make the meaning clear:

▪ Statistical Significance:

• Exposure to the health care system was a significant protective factor for exclusive throat carriage of Staphylococcus aureus (odds ratio, 0.67; P = .001).

• Most associations remained statistically significant at the adjusted significance level (P < .125).

▪ Clinical Significance:

• Low creatinine values in patients with connective tissue diseases were found to be clinically significant.

• The combination of erythromycin and carbamazepine represents a clinically significant drug interaction and should be avoided when possible.

▪ Worthy/Important:

• His appointment as chair of the department was a significant victory for those who appreciated his skill in teaching.

• A journal’s 100th anniversary is significant and should be celebrated.

Sometimes, however, the context does not clarify the meaning and ambiguity results.

▪ The one truly significant adverse effect that has caused carbon dioxide resurfacing to lose favor is hypopigmentation, which can be unpredictable and resistant to treatment.

To avoid the possibility of ambiguity, some have recommended confining the word to only one of its meanings. However, why cheat a word of one of its legitimate meanings when there are ways to retain its richness and yet not confuse the reader?—Cheryl Iverson, MA

# Bucking the “Trend” and Approaching “Approaching Significance”

I believe we are on an irreversible trend toward more freedom and democracy – but that could change.

—Dan Quayle

In general usage, the concept of trend implies movement. Not only is this implied in its definitions, but the word can be traced to its Middle High German root of trendel, which is a disk or spinning top.1

In scientific writing, when is a trend not a trend? When it is not referring to comparisons of findings across an ordered series of categories or across periods of time. However, this and related terms are often misused in manuscripts and articles.

Most studies are constructed as hypothesis testing. Because an individual study only provides a point estimate of the truth, the researchers must determine before conducting the study an acceptable cutoff for the probability that a finding of an association is due to chance (the α value, most commonly but not universally set at .05 in clinical studies). This creates a dichotomous situation in interpreting the result: the study either does or does not meet this criterion. If the criterion is met, the finding is described as “statistically significant”; if it is not met, the finding is described as “not statistically significant.”

There are many limitations to this approach. Where the α level is set is arbitrary; therefore, in general all findings should be expressed as the study’s point estimate and confidence interval, rather than just the study estimate and the P value. Despite the limitations, if a researcher designs a study on the basis of hypothesis testing, it is not appropriate to change the rules after the results are available, and the results should be interpreted accordingly. The entire study design (such as calculation of the sample size and study power – the ability of a study to detect an actual difference or effect, if one truly exists) is dependent on setting the rules in advance and adhering to them.

If a study does not meet the significance criterion (for example, if the α level was set as < .05, and the P value for the finding was .08), authors sometimes describe the findings as “trending toward significance,” “having a trend toward significance,” “approaching significance,” “borderline significant,” or “nearly significant.” None of these terms is correct. Results do not trend toward significant—they either are or are not statistically significant based on the prespecified study assumptions. Similarly, the results do not include any movement and so cannot “approach” significance; and because of the dichotomous definition, “nearly significant” is no more meaningful than “nearly pregnant.”

When a finding does not meet statistical significance, there are generally 2 possible explanations: (1) There is no real association. (2) There might be an association, but the study was underpowered to detect it, usually because there were not enough participants or outcome events. A finding that does not meet statistical significance may still be clinically important and warrant further consideration.

However, when authors use terms such as trend or approaching significance, they are hedging the interpretation. In effect, they are treating the findings as if the association were statistically significant, or as if it might have been if the study had just gone a little differently. This is not justified. (Lang and Secic2 make the fascinating observation that “Curiously, P values never seem to ‘trend’ away from significance.”)

A proper use of the term trend refers to the results of one of the specific statistical tests for trend, the purpose of which is to estimate the likelihood that differences across 3 or more groups move (increase or decrease) in a meaningful direction more than would be expected by chance. For example, if a population of persons is ranked by evenly divided quintiles based on serum cholesterol level (from lowest to highest), and the risk of subsequent myocardial infarction is measured in each group, the researcher may want to determine whether risk increases in a linear way across the groups. Statistical tests that might be used for analyzing trends include the χ2 test for trend and the Cochran-Armitage test.

Similarly, a researcher may want to test for a directional movement in the values of data over time, such as a month-to-month decrease in prescriptions of a medication following publication of an article describing major adverse effects. A number of analytic approaches can be used for this, including time series and other regression models.

Instead of using these terms, the options are:

1. Delete the reported finding if it is not clinically important or a primary outcome. OR

2. Report the finding with its P value. Describe the result as “not statistically significant,” or “a statistically nonsignificant reduction/increase,” and provide the confidence interval so that the reader can judge whether insufficient power is a likely reason for the lack of statistical significance.

If the finding is considered clinically important, authors should discuss why they believe the results did not achieve statistical significance and provide support for this argument (for example, explaining how the study was underpowered). However, this type of discussion is an interpretation of the finding and should take place in the “Discussion” (or “Comment”) section, not in the “Results” section.

Bottom line:

1. The term trend should only be used when reporting the results of statistical tests for trend.

2. Other uses of trend or approaching significance should be removed and replaced with a simple statement of the findings and the phrase not statistically significant (or the equivalent). Confidence intervals, along with point estimates, should be provided whenever possible.—Robert M. Golub, MD

1. Mish FC, ed in chief. Merriam-Webster’s Collegiate Dictionary. 11th ed. Springfield, MA: Merriam-Webster Inc; 2003.

2. Lang TA, Secic M. How to Report Statistics in Medicine: Annotated Guidelines for Authors, Editors, and Publishers. 2nd ed. Philadelphia, PA: American College of Physicans; 2006:56, 58.

# Incidence

In medical contexts, incidence is most often used in its epidemiologic sense, ie, the number of new cases of a disease occurring over a defined period among persons at risk for that disease. When thus used, incidence may be expressed as a percentage (new cases divided by number of persons at risk during the period) or as a rate (number of new cases divided by number of person-years at risk).

Reporting several incidence values in the same sentence can nearly always be accomplished using the singular form (eg, “the incidence of nonfatal myocardial infarction during follow-up was 10% at 6 months, 19% at 12 months, and 26% at 18 months” or “the incidence of clinical stroke decreased significantly, from 7.6 to 5.3 per 1000 person-years in men and from 6.2 to 5.1 per 1000 person-years in women). However, in rare instances, sentence construction may necessitate the use of the plural, which of course is… what, exactly? The understandable urge to simply add an “s” at the end of the word to form the plural results in incidences — a form not found in most dictionaries and a clunker of a word if ever there was one. Writers wishing for a more mellifluous plural sometimes use incidence rates, a valid term but one perhaps best reserved for reporting incidence values expressed as actual rates rather than simple percentages. Moreover, incidences is sometimes used when reporting values either as percentages or as rates, in the latter case missing a valuable opportunity to emphasize that rates rather than percentages are being reported.

Thus, it is perhaps best to use incidences, awkward as it may be, when reporting multiple incidence values as percentages and incidence rates when reporting such values as rates, eg, “at first follow-up, the incidences of falls resulting from frailty, neuromuscular disorders, or improper use of mobility devices were 15% (95% CI, 10%-20%), 12% (95% CI, 7%-17%), and 12% (5%-19%), respectively” or “the incidence rates for falls resulting from frailty, neuromuscular disorders, or improper use of mobility devices were 5.1, 6.3, and 4.6 per person-year, respectively.” Incidentally, these 2 examples report occurrences (falls) rather than diseases or conditions, and so represent 2 instances reporting the incidence of incidents.

To further muddy the waters, incidence is sometimes confused with prevalence, defined as the proportion of persons with a disease at any given time (ie, total number of cases divided by total population). Thus, whereas incidence describes how commonly cases are diagnosed, prevalence describes how widespread the disease already is; on a more personal level, incidence describes one’s risk of developing the disease, whereas prevalence describes the likelihood that one already has it. The confusion between the terms is perhaps attributable to the occasional use of prevalence in place of incidence in the study of rare, chronic diseases for which few newly diagnosed cases are available; however, this circumstance is unusual, and incidence and prevalence should always be distinguished from one another and used appropriately. (See also §20.9, Glossary of Statistical Terms, in the AMA Manual of Style, p 872 in print.)

Whereas prevalence is often used in general contexts to indicate predominance or general acceptance, the circumstances calling for the use of incidence in general contexts are quite few and become fewer still when one takes into account that incidence is often used when incidents (the simple plural of incident) or instance (again denoting an occurrence) would be the better choice. Perhaps incidents or instances was intended but never made it to the page — as is so often the case with homophones and near-homophones, even the careful writer who usually would not confuse incidence, incidents, and instance might one day look back over a hastily typed passage only to see that a wayward incidence has crept in; if the passage is hastily edited to boot, the error might well go unnoticed until the passage is in print and a discerning reader takes pains to point it out in a letter or e-mail. The plural form, incidences, has virtually no use outside of the epidemiologic discussed above, although it has been used to subtly disorienting effect by translators rendering the Kafkaesque works of Russian writer Daniil Kharms (1904-1942) into English, most notably when rendering the 1-word title of Incidences, Kharms’ 1934 collection of absurdist critiques on life in the Soviet Union under Stalin. However, writers who are not political dissidents aiming for absurdist effect — presumably all medical writers — would do well to proofread carefully and often. — Phil Sefton, ELS

# Questions From Users of the Manual

Q: If a product name appears in all caps in a company’s product literature (with or without a trademark symbol or registered symbol), must the editor retain the all caps in a journal article? Companies use caps for graphic impact or emphasis, but caps can be distracting and can make the text difficult to read. Would it be acceptable to substitute only an initial cap for an all-cap product name, particularly if the product is the main subject of the manuscript and occurs frequently?

A: Our journals do not require use of the trademark symbol (™) or the registered symbol (®) as the use of the initial cap frequently used on proprietary names indicates the proprietary nature of the name (see 5.6.16, Legal and Ethical Considerations, Intellectual Property:  Ownership Access, Rights, and Management, Trademark). There are exceptions to the use of the initial cap (eg, pHisoHex; see section 10.8, “Intercapped” Compounds) and in these cases, as in all others, we advise using the name according to the presentation of the legal trademark. To avoid a plethora of caps—which certainly can be distracting—we would suggest varying the way in which the product is referred to (eg, “this product,” “it”) as long as the meaning remains clear.

Q: Your manual indicates that references should be numbered consecutively with arabic numerals in the order in which they are cited in the text. But what about the distinction between references cited in a range and references cited individually? If an author cites references 1 through 5, does this count as only the citation of reference 1, as the first number in the range, or does it count as citation of all 5 references included in the range?

A: It matters not if the references are cited as part of a range or cited individually. Even if a reference is cited as part of a range, when any one of those references is cited later, it retains the same reference number.  This is not specifically stated in the Manual and, perhaps wrongly, we assumed that it would be understood. Thank you for allowing us to clarify this point.

Q: Convention seems to be to use the leading zero in P values, but why is this necessary since P cannot be greater than 1?

A: JAMA and the Archives Journals do not use a zero to the left of the decimal point, since statistically it is not possible to prove or disprove the null hypothesis completely when only a sample of the population is tested (P cannot equal 1 or 0, except by rounding). If convention dictates otherwise, we are unconventional!

Q: I have been unable to find specific rules on the use of nonbreaking hyphens and spaces. Do you have any suggestions for the correct and preferred use of nonbreaking hyphens and spaces?

A: You are right. We do not have any section devoted to this. However, there is information about line breaks scattered throughout the Manual. For example:

• On page 29 (section 1.20.4), there is information on how to break an e-mail address. The same guidelines apply to breaking URLs.
• On page 646 (section 15.6.4), there is information on breaking long karyotypes.
• On page 910 (section 21.5), there is information on breaking long formulas.

There may be other instances like this scattered throughout the Manual where specific guidance is needed. However, individual publishers or clients may have their own preferences that require attention when editing material for their publications.

Q: I am working on a manuscript in which one of the authors has listed the degree MAS (Master of Advanced Studies). This abbreviation is not included in the Manual. Is it acceptable?

A:  This is a perfectly acceptable abbreviation. We simply did not have space to list all possible degrees and their abbreviations in the Manual and attempted to list some of the more common ones.—Cheryl Iverson, MA