Running head: CHAPTER 3 1

IV Acetaminophen Research Proposal Chapter 3

Cathy Bozek, Karen Collins, Beth Kalkman, Lori Van Zoeren, and Joel Vedders

Ferris State University

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IV Acetaminophen Research Proposal Chapter 3

For more than ten weeks, the research team consisting of Bozek, Collins, Kalkman,

VanZoeren, and Veddershas compiled data to rationalize the need for a research study to validate

our proposed hypothesis that the use of IV acetaminophen in the elderly post-operative hip

fracture patient is expected to decrease the consumption of opioids. Chapter 1of the proposal

focused on the introduction to our research project. An abbreviated literature review was

performed based upon our stated hypothesis; the research question was identified; and, a

theoretical framework was chosen and discussed.

In Chapter 2, a comprehensive literature review provided a detailed explanation of the

key concepts related to the proposed study. Gaps in the research were revealed related to the

elderly hip fracture population and optimal standards to treatpain. In addition, there were limited

studies comparing IV versus oral acetaminophen using a multimodal approach. This confirmed

the use of Good and Moore's (1996)theoretical framework pain: a balance between analgesia

and side effects (BASE) as an appropriate choice to test the hypothesis. It is believed that a

multi-modal approach to pain control will have an effect on outcome measures for these patients

including decreased untoward side effects, decreased length of hospital stay, earlier ambulation,

and optimal post-operative functioning.

In Chapter 3, the focus will be on the design and methodology of the proposed study.

The specific research design, sampling plan and method of data collection will be addressed.

Additionally, reliability and validity of the chosen instruments will be discussed. As in any

research study, we will present the limitations and ethical concerns of this proposal.It will be

imperative to choose the proper design and methods to carry out accurate data collection that is

untainted with excessiverigor.By the end of this final chapter, the reader should have a clear

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understanding of the entire research proposal and the planned methods for conducting the

research.

Research Design

The study we are proposing is one of experimentation; more specifically, we are planning

a type of quantitative research design known as a three-armed, double-blind, placebo controlled

randomized controlled trial(RCT). In a RCT, participants are randomly assigned to two or more

groups; one group receives standard treatment and the other group (or groups) receives the

experimental intervention (Stanley, 2007). There are three defining characteristics of a RCT:

manipulation, control, and randomization (Polit&Beck, 2012). We will be determining the effect

of manipulating the route of acetaminophen administration on opioid consumption in the chosen

population for 48 hours post-operatively. In addition, we will be providing a counterfactual (or

control group) which helps to validate the relationship between the independent and dependent

variables by removing the independent variable from one group in the sample (Polit&Beck,

2012). By including a non-intervention group, we can better determine that the observed results

are attributable to the independent variable (Polit&Beck, 2012). Furthermore, we will randomly

assign subjects from the study sample to one of three groups: IV administration of

acetaminophen, oral administration of acetaminophen, or no acetaminophen administration.

Randomization helps to remove the potential for researcher bias (Stanley, 2007; Wood & Ross-

Kerr, 2011).

To double-blind this study, where caregiver and patient are unaware of the treatment

assignment (Polit&Beck, 2012), it will be necessary for all participants to receive IV and oral

"medication" simultaneously every six hours. For two of the groups, one route will contain

acetaminophen whereas the other will contain a placebo. In the control group, neither route will

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contain acetaminophen. Providing the intervention in this manner will protect against the

Hawthorne effect, an elevated response due to participation in a research study (Polit& Beck,

2012). All other care provision will be identical between groups.

An area of consideration in an RCT is the principle of clinical equipoise(Stanley, 2007).

Under this ethical principle, a researcher cannot intentionally submit research participants to

interventions which are knowingly sub-standard (Stanley, 2007). Therefore, all groups within a

study must receive treatment that is, at the minimum, provided at the current accepted standard

of care. Because the literature supports opioids in standard pain management following

orthopedic surgery (Vadivelu, Mitra, & Narayan, 2010), opioids will be available and utilized

within our study. The question our research seeks to answer is whether intravenous

acetaminophen will decrease the use of opioids in the target population.

Setting and Sample

Setting

The setting for our proposed research study is a dedicated orthopedic care unit

specializing in fracture repair located at a Level 1 regional trauma center in West Michigan. It is

estimated that this facility repairs more than 400 intertrochanteric (IT) fractures every year

providing a sufficiently large population from which to recruit our study sample. Furthermore,

this trauma center is known for its on-going participation in research and its provision of state-

of-the-art care. Performing our proposed research in this single-site setting will lend credibility

to our proposed research, ease sample recruitment, result in consistent quality service to study

participants, and also provide a supportive environment for novice researchers.

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Sample

As stated in the research hypothesis, our population of interest is the elderly (age 65 and

older) hip fracture patient. Polit and Beck (2012) emphasize that a target population is best

represented by a sampling which accurately reflects the common features of the desired group.

Chapter 2 of our proposal clearly describes the unique characteristics of the elderly. Inclusion of

these characteristics will be intentional during the recruitment process thereby strengthening the

study's external validity (Wood & Ross-Kerr, 2011).

Conversely, in order to strengthen the internal validity of our study, some variability

within the sample must be controlled (Polit&Beck, 2012). For example, there are a variety of

orthopedic repair techniques which differ in degree of invasiveness based on the presentation of

the hip fracture. To decrease the potential risk of study results being attributed to variations in

methods of repair, only those patients undergoing an open reduction internal fixation (ORIF) for

an IT fracture will be eligible for study inclusion. After careful consideration by the research

team the following eligibility criteria have been determined:

Inclusion criteria:

1. Age: 65 years and older.

2. Gender: Male or female.

3. Race: No limitation.

4. Cognition: Alert and oriented as determined by a satisfactory score on the Mini-

Mental State Exam (MMSE) (see Appendix A).

5. Social: Family support identified.

6. Nutritional status: Adequate.

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7. Medication: No allergies to acetaminophen or opioids. No identified potential drug-

drug interactions between acetaminophen or opioids and patient's current medication

list.

8. Injury: Isolated IT fracture.

9. Literacy: English speaking and/or reading, or ability to give informed consent

through use of interpretive services.

Exclusion criteria:

1. The inverse to any of the above criteria.

2. Current treatment with opioids for conditions such as chronic pain.

3. Existence of severe liver disease.

4. Inability to swallow.

Regulatory criteria:

1. The study must have signed approval by the appropriate governing body at the

proposed research site. If Institutional Review Board (IRB) approval is deemed

necessary, this will be achieved and documented.

2. A signed informed consent must be documented and kept available for each study

participant.

3. Ethical concerns must be addressed and have satisfactory resolution prior to

conducting the study (Wood & Ross-Kerr, 2011).

Intact cognition will be determined through the administration of the MMSE by

individuals trained in the administration and scoring of this test. This 10-15 minute test includes

examination of memory, orientation, attention, recall and abstract thinking (Feliciano, Baker,

Anderson, LeBlanc, &Orchanian, 2011). The MMSE has been extensively researched and

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validated with "interrater correlations of r=.82 and test-retest reliability ranging from r=.89 to

r=.98 and sensitivity and specificity rates of 71% and 95.6% in hospitalized patients" (Feliciano

et al., 2011, p.2). Due to the administration time of this test being considerably less than that of

another commonly used test, the Cognitive Assessment of Minnesota (CAM) which takes 35-45

minutes to administer (Feliciano et al., 2011, p.2), the choice was made to use the MMSE.

Because we have identified a specific setting for this study and we have a target

population of the elderly hip fracture patient, consecutive sampling will be used to obtain the

necessary subjects. A power analysis will be performed by a research statistician to determine

the necessary sample size. Per Polit and Beck's (2012) definition of consecutive sampling, all

individuals who present to the trauma center during sample recruitment and meet the eligibility

criteria for the study will be approached for study inclusion. All information related to the study

will be discussed with the individual in order to obtain informed consent. Once consent is

gained, the patient will be enrolled in the study and randomized into a particular treatment group.

Methods

In order to have a study that is free of bias, blinding must occur. Blinding eliminates

three types of bias.The first type is expectation bias; if the patient is unaware of which drug is

being administered the outcome cannot be influenced by the patient's expectation of its efficacy

(Polit& Beck, 2012, p.212). Secondly, performance bias is eliminated; if the care provider is

unaware of which agent is being administered, it will eliminate differences in care provided to

different groups (Polit& Beck, 2012). For example, if the nurse was aware the patient was

receiving placebo only, he or she may implement other methods of pain control such as ice to the

surgical site, or spend more time teaching relaxation techniques.The third type of bias, detection

bias, will be controlled by utilizing the Numeric Rating Scale (NRS) to measure pain which

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allows no room for recording variations in outcome variables. This method provides

transparency which allows for multiple researchers to deliver the same method of assessment and

acquire the same results (Burns & Groves, 2007).

Study Variables

Post-operative order sets will be developed for the purpose of the study through a

collaborative effort by the orthopedic surgeons, nursing staff, and researchers. The orders will

include routine post-operative orthopedic orders with the addition of the administration of the

randomized intervention. The primary investigator (PI) will draw an envelope containing post-

operative orders from a box holding the appropriate number of envelopes as determined by the

power analysis.

Once the patient is awake, alert, and able to swallow pills following surgery, he or she

will receive administration of the first randomly assigned dose as determined by the post-op

orders. The pharmacy will then be notified of the time of administration of this initial dose and

will schedule consecutive doses every six hours for 48 hours on the electronic medication

administration record (EMAR). Prior to the administration of each dose the patient's pain will be

assessed and recorded using the eleven point NRS with numbers ranging from zero to ten. Zero

represents no pain while ten represents the worst pain possible(see Appendix B).

  According to Hawker, Mian, Kendzerska, and French (2011), the advantage of the NRS

scale over the visual analog scale (VAS) is its simplicity, scoring, and the fact that it can be

administered both verbally and in writing. It also takes less time to administer, is easy to

complete, and can be used across cultures and languages (2011). The NRS has also shown high

reliability and validity. "High test-retest reliability has been observed in both literate and

illiterate patients. For construct validity, it is shown to be highly correlated to the VAS"

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(Hawker et al., 2011, p. 242).Hjermstad et al. (2011) echo those results; the NRS and the VAS

were viewed as the most reliable and easiest to use. According to Flaherty (2012), the NRS is the

most widely utilized pain intensity scale administered in older adults. We, therefore, felt this

measurement tool was best suited for our study.

The patient's pain will also be scored and recorded 30 minutes after administration of the

study dose in theelectronic medical record (EMR).Additionally, the facility'sroutine ongoing

pain assessment protocols will be followed. Opioids will be administered for further pain control

when requested by the patient. Opioid usage during the 48 hour postoperative period will be

tallied from the EMR.The PI will be able to gather this information by chart review after the 48

hour time frame has ended. This information will then be submitted for data analysis.

Data Analysis

Through a power analysis, we expect to recruit a large enough sample size to use the

multivariate analysis of variance (MANOVA) to analyze and compare the data. MANOVA is an

extension of the analysis of variance (ANOVA); the parametric procedure for testing differences

between means when there are at least three groups to be studied (Polit& Beck, 2012).

MANOVA will also increase control for the proposed research, due to its ability to look at the

significance of the differences between dependent variables (Polit& Beck, 2012). MANOVA

compares the significance of differences for multiple dependent variables (Polit& Beck, 2012, p.

446). If, as per the guidance of an experienced researcher, we are unable to obtain the necessary

sample size, a simple ANOVA will be performed (Ford, personal communication, April 15,

2013). Utilization of a double-blind technique will have patients serve as their own controls for

the comparison between the two routes of administration of acetaminophen.

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In addition to pain and opioid use, data will be extracted from the EMR related to falls,

constipation, delirium, nausea and vomiting. Data will be entered into the most current addition

of the Statistical Package for the Social Sciences (SPSS). A paid researcher familiar with this

software will enter the data. Descriptive statistics will compare the mean, mode, and median of

the amounts of rescue opioids used in conjunction with the route of acetaminophen or placebo.

By utilizing SPSS to input data and perform a two-tailed test, we will test at the 0.05 level of

significance.  Rejection of our null hypothesis will occur if the results are greater than 0.05

(Polit&Beck, 2012, p.409). We can also run a multiple linear regression in SPSS to view the

relationship between the multiple variables or provide scatter plots which will show the

relationship between the independent and dependent variables.

Reliability and Validity

A Level III research study“demands the highest degree of validity and reliability testing”

(Wood & Ross-Kerr, 2011, p. 203). For this reason, we have chosen to utilize well-known

measurement tools that have been tested and proven to be reliable and valid.Reliability is the

“degree of consistency or dependability with which an instrument measures an attribute” (Polit&

Beck, 2012, p. 741).  This equates to the measure’s stability, consistency, or dependability.

These components need to be accurate for the study to be reproducible. Validity is a quality

criterion referring to the degreeby which inferences made in a study are accurate and well

founded (Polit& Beck, 2012).  Validity in measurement is the “degree to which an instrument

measures what it is intended to measure” (Polit& Beck, 2012, p. 745). 

In this proposed study, control of experimental conditions will be enhanced by keeping

procedures as consistent as possible. For example, as we are focusing our study on one type of

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hip fracture repair, ORIF of an IT fracture, discrepancies in surgical technique will be

minimized.  Equipment will also remain constant. 

In addition, we will utilize a well-known pain scale. The NRS has been chosen due to its

ease in use with both the patients and the nursing staff. The reliability and validity of the NRS

was discussed earlier in this paper, on page 8. The nursing staff will receive instruction by one

trainer regarding the utilization of the NRS pain scale and the importance of documenting pain

accurately throughout the pre- and post-intervention periods. Using one trainer will decrease

teaching bias among several different trainers.   

Another measurement tool, the Confusion Assessment Method (CAM), will be used to

detect delirium among our chosen population post-operatively (see Appendix C).  The CAM tool

is valid and shows high interrater reliability (kappa=0.79-0.96) (Tate&Happ, 2012, para 4).  This

test is also easy to administer with minimal training.  Testing time is about 2 minutes

(Tate&Happ, 2012). Both the NRS and the CAM scales will be serially addressed at regular

prescribed intervals and documented in the EMR. 

Limitations

Despite careful preparation and planning, there will be questions that remain unanswered

after conducting a research study. It is important for researchers to have appropriate

expectations for their work.This requires a discussion related to the potential limitations of the

research proposal. For example, limitations of this study include the possibility that despite

training and education of nursing staff and test administrators related to the goals of this study,

there may still be variance in administration of the intervention, patient assessment, and

documentation of study data.

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Due to the age of our sample population, attrition is also a very real threat to this study's

success. Although efforts have been made through the inclusion criteria to reduce the risk of

attrition, there still remains the possibility that untoward events will cause unavoidable removal

from the study. Possible reasons for removal include intolerance of medication administration,

error in medication administration, unforeseen medical events, development of delirium, or

death.

In addition, this study is targeted to the elderly population. Reasons for this have been

validated in earlier chapters of this study proposal. This does mean, however, that findings from

this study may not be applicable to people of different age groups.Additional limitations may be

discovered after completion of the study and analysis of the data.

Ethical Concerns

When performing research on human beings, especially a vulnerable population such as

the elderly, there are ethical concerns to be considered. Involved with this, is the safeguarding of

ethical concepts such as beneficence, preservation of human dignity, and justice (Polit& Beck,

2012). The authors of this research proposal will ensure that the study is performed with the

utmost integrity by qualified personnel.

Informed consent will be obtained in writing after full disclosure of the study's purposes

has occurred. Potential participants will have the opportunity to ask questions and request

clarification related to the study before signing consent. Participants will also be fully aware of

their right to withdraw from the study at any time without question. Participants will be asked to

grant permission for dissemination of study results, should this study be recommended for

publication.

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As within any healthcare system, confidentiality of patient information and privacy will

be maintained.Participant anonymity will be further protected by assigning identification

numbers to de-identify individual patient data for reference purposes during data extraction from

the EMR.The PI will take the obtained information and deliver it to the paid research statistician

who will have signed an agreement of confidentiality prior to handling study data.

In addition, the researchers believe the results of this study to be of potential significant

benefit to the elderly hip fracture population. Standard post-operative pain management will not

be withheld from these patients thereby protecting subjects from clinical equipoise. Rather, by

adding IV acetaminophen as an adjunct therapy, we believe there will be a change in post-

operative opioid usage.

Finally, as previously stated in the text, the proposal will be submitted for review to the

IRB of the proposed study site. The IRB of any facility conducting a research study must

approve all research prior to implementation to safeguard patient protection and the ethical

integrity of the research (ANA, 2010). This board, consisting of experts in research and risk

management, will examine the proposal to disclose any unaddressed ethical concerns specific to

performing this study on the elderly hip fracture population. Any identified concerns will be

corrected by the researchers prior to re-submission of the proposal for IRB approval.

Summary

In summary, Chapters 1 and 2 have developed rationale for our research proposal in

depth. A hypothesis has been developed, research questions posed, literature reviewed,

significant variables discussed, and a theoretical framework created. Now, in Chapter 3,

specifics related to the research design, methods, setting and sample including inclusion criteria,

data analysis, reliability and validity of our chosen tools, limitations, and ethical considerations

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have been addressed. It is the opinion of these authors that this research proposal has the

potential to provide valuable information to ensure evidence based care for this vulnerable

population.

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References

American Nurses Association (ANA, 2010). Guide to the code of ethics for nurses: interpretation

and application. Silver Spring, MD: Nursesbooks.org.

Burns, N., & Groves, S. K. (2007). Understanding nursing research (4th ed.). St Louis, MO:

Sanders Elsevier.

Feliciano, L., Baker, J. C., Anderson, S. L., LeBlanc, L. A., &Orchanian, D. M.

(2011).Concurrent validity of the cognitive assessment of Minnesota in older adults with

and without depressive symptoms.Journal of Aging Research, 2011, 1-6.

http://dx.doi.org/10.4061/2011/853624

Flaherty, E. (2012). Best practices in nursing care to older adults. Retrieved from

http://consultgerirn.org/uploads/File/trythis/try_this_7.pdf

Hawker, G. A., Mian, S., Kendzerska, T., & French, M. (2011).Measures of adult pain. Arthritis

Care and Research, 63(11), 240-252. http://dx.doi.org/10.1002/acr.20543

Hjermstad, M. J., Fayers, P.M., Haugen, D. F., Carceni, A., Hanks, G. W., Loge, J. H., Kaasa, S.

(2011). Studies comparing numerical rating scales for assessment of pain intensity in

adults: a systematic literature review. Journal of Pain and Symptom Management, 41,

1073-1092. http://dx.doi.org/10.1016/j.jpainsymman.2010.08.016

Polit, D. F., & Beck, C. T. (2012). Nursing research: Generating and assessing evidence for

nursing practice (9th ed.). Philadelphia, PA: Lippincott, Williams & Wilkins.

Stanley, K. (2007). Statistical primer for cardiovascular research: Design of randomized

controlled trials. Circulation, 115, 1164-1169.

http://dx.doi.org/10.1161/CIRCULATIONAHA.105.594945

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Tate, J. A., &Happ, M. B. (2012).The confusion assessment method for the ICU (CAM-ICU)

[Issue brief 25]. Retrieved from The Hartford Institute for Geriatric Nursing, New York

University, College of Nursing. www.harfordign.org

Vadivelu, N., Mitra, S., & Narayan, D. (2010). Recent advances in post-operative pain

management. Yale Journal of Biology and Medicine, 83, 11-25.

Wood, M. J., & Ross-Kerr, J. C. (2011). Basic steps in planning nursing research:  From

question to proposal (7th ed.). Sudbury, MA: Jones and Bartlett.

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Appendix A

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Appendix B

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Appendix C

The Confusion Assessment Method Instrument:1. [Acute Onset] Is there evidence of an acute change in mental status from the patient’s baseline?2A. [Inattention] Did the patient have difficulty focusing attention, for example, being easily distractible, or havingdifficulty keeping track of what was being said?2B. (If present or abnormal) Did this behavior fluctuate during the interview, that is, tend to come and go orincrease and decrease in severity?3. [Disorganized thinking] Was the patient’s thinking disorganized or incoherent, such as rambling or irrelevantconversation, unclear or illogical flow of ideas, or unpredictable switching from subject to subject?4. [Altered level of consciousness] .Overall, how would you rate this patient’s level of consciousness? (Alert[normal]; Vigilant [hyperalert, overly sensitive to environmental stimuli, startled very easily], Lethargic [drowsy,easily aroused]; Stupor [difficult to arouse]; Coma; [unarousable]; Uncertain)5. [Disorientation] Was the patient disoriented at any time during the interview, such as thinking that he or she wassomewhere other than the hospital, using the wrong bed, or misjudging the time of day?6. [Memory impairment] Did the patient demonstrate any memory problems during the interview, such as inabilityto remember events in the hospital or difficulty remembering instructions?7. [Perceptual disturbances] Did the patient have any evidence of perceptual disturbances, for example,hallucinations, illusions or misinterpretations (such as thinking something was moving when it was not)?8A. [Psychomotor agitation] At any time during the interview did the patient have an unusually increased level ofmotor activity such as restlessness, picking at bedclothes, tapping fingers or making frequent sudden changes ofposition?8B. [Psychomotor retardation].At any time during the interview did the patient have an unusually decreased levelof motor activity such as sluggishness, staring into space, staying in one position for a long time or moving veryslowly?9. [Altered sleep-wake cycle]. Did the patient have evidence of disturbance of the sleep-wake cycle, such asexcessive daytime sleepiness with insomnia at night?

The Confusion Assessment Method (CAM) Diagnostic AlgorithmFeature 1: Acute Onset and Fluctuating CourseThis feature is usually obtained from a family member or nurse and is shown by positive responses to the followingquestions: Is there evidence of an acute change in mental status from the patient’s baseline? Did the (abnormal)behavior fluctuate during the day, that is, tend to come and go, or increase and decrease in severity?Feature 2: InattentionThis feature is shown by a positive response to the following question: Did the patient have difficulty focusingattention, for example, being easily distractible, or having difficulty keeping track of what was being said?Feature 3: Disorganized thinking

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This feature is shown by a positive response to the following question: Was the patient’s thinking disorganized orincoherent, such as rambling or irrelevant conversation, unclear or illogical flow of ideas, or unpredictable switchingfrom subject to subject?Feature 4: Altered Level of consciousnessThis feature is shown by any answer other than “alert” to the following question:Overall, how would you rate this patient’s level of consciousness? (alert [normal]), vigilant [hyperalert], lethargic[drowsy, easily aroused], stupor [difficult to arouse], or coma [unarousable])The diagnosis of delirium by CAM requires the presence of features 1 and 2 and either 3 or 4.CAM Instrument and Algorithim adapted from Inouye, S., van Dyck, C., Alessi, C., Balkin, S., Siegal, A. &Horwitz, R.(1990). Clarifying confusion: the confusion assessment method. Annals of Internal Medicine, 113(12), 941-948.