J Manipulative Physiol Ther. 2015 (Nov); 38 (9): 692–698 ~ FULL TEXT
Aurélie M. Marchand, DC, MScACPP
Doctor of Chiropractic,
OBJECTIVE: The purpose of this study was to perform a literature search to identify relevant studies on pediatric spinal manipulation and chiropractic manipulative therapy and to assess if safety terminology was consistent with the International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH).
METHODS: A literature search was performed in PubMed using the following terms: spinal manipulation pediatric, chiropractic safety pediatric, and manual therapy safety pediatric. PubMed was searched from inception to April 2012 with no language limitations. The international standards included the terminology of the World Health Organization on side effects, adverse reactions, adverse events and the ICH guideline templates that were adapted for manual therapy for this study.
RESULTS: Of the 9 relevant articles identified in this study, 3 reported methodology for classifying safety incidents, and all 9 used safety terminology (adverse effects or adverse events). However, terminology was not used consistently.
CONCLUSION: Most of the articles identified in this literature review did not use terminology consistent with the standards established by the ICH when reporting on safety incidents following pediatric spinal manipulation or chiropractic manipulative therapy. More efforts should be taken to include consistent terminology for studies of spinal manipulation and chiropractic manipulative therapy for children.
KEYWORDS: Children; Chiropractic; Manual Therapy; Pediatrics; Safety
From the Full-Text Article:
Chiropractic care, including spinal manipulation, is commonly used in the management of pediatric spinal, musculoskeletal, and nonmusculoskeletal complaints. [1-3] Conditions such as back pain have been shown to be prevalent in the pediatric population and leading to recurrence of episodes in adulthood. [2, 4-6]Pediatric chiropractic research is currently emergent with descriptive studies including few observational studies and clinical trials looking at the effectiveness of chiropractic treatment for specific conditions.  The safety of manual therapy as a treatment approach has also received increased attention in the last decade. [1, 2, 7] Several studies providing primary data on the occurrence of safety incidents after pediatric manual therapy have used inconsistent safety terminology. [1, 7-11] Despite the small amount of information currently available on this topic, 2 systems of classification for safety incidents have been proposed. [1, 12, 13]
Lack of consistency in reporting information on adverse reactions/events may lead to confusion regarding the type of safety incident occurring. Investigating and reporting safety incidents will ultimately improve the care provided to patients by allowing appropriate identification and management of known risks.  Therefore, understanding international standards in terminology, procedures, and requirements in medical patient safety such as those offered by the International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH) may offer better consistency. The use of internationally agreed terminology and reporting procedures should allow better intra- and interprofessional understanding and sharing of information on the safety of chiropractic pediatric care. Therefore, the purposes of this study were to perform a literature search to identify relevant studies on pediatric spinal manipulation and chiropractic manipulative therapy and to assess if safety terminology was consistent with categories suggested by the ICH.
Reporting safety incidents is crucial to promoting better understanding of which procedures may be at risk of causing and/or which patients may be at higher risk for developing adverse reactions with the aim to improve the safety of clinical procedures in the future.  Medical surveillance programs investigating the safety of complementary and alternative medicines have pointed at the importance of misdiagnosis, delayed diagnosis, and failure to use conventional medicine with serious consequences for pediatric patients. [19-21] The risk of misdiagnosis and delayed appropriate care could be diminished if practitioners followed the best practices recommendations for chiropractic care in the pediatric population.  It is beyond the scope of this article to review the evidence on pediatric chiropractic safety reports that has been recently been previously addressed. [1, 7] The aim is to address the data gathering and reporting processes along with addressing terminology in safety incidents.
One classification system of pediatric safety incidents considers the severity of adverse events1; another considers the severity and the time lapse of safety incidents. [12, 13] The first classification divides safety incidents as an occurrence of adverse events.1 There are 4 categories: mild (self-limited, not requiring additional medical care), moderate (transient disability requiring medical care but no hospitalization), severe (permanent disability requiring hospitalization or death), and a category for adverse events caused by delayed diagnosis or misdiagnosis. The second classification created by a consensus process classifies safety incidents as adverse events and divides them into 3 categories.  The first category includes major adverse events (medium to long term, moderate to severe, and unacceptable events that normally require further treatment and are serious and distressing); the second category regroups moderate adverse events (similar to major adverse events but only moderate in severity); and the third category regroups mild and not adverse events (short term and mild, nonserious, where the patient's function remains intact, and adverse events are transient/reversible; no treatment alterations are required because the consequences are short term and contained). 
The terminology used by WHO to describe safety incidents are adverse reaction, adverse event, and side effect. An adverse reaction is “a response to a drug which is noxious and unintended, and which occurs at doses normally used in man for the prophylaxis, diagnosis, or therapy of disease, or for the modification of physiological function.” An adverse event is “any untoward medical occurrence that may present during treatment with a pharmaceutical product but which does not necessarily have a causal relationship with this treatment.” A side effect is “any unintended effect of a pharmaceutical product occurring at doses normally used in man which is related to the pharmacological properties of the drug.”  Based on these definitions, the terminology reported in the articles relevant to the search was not congruent with the use of the term adverse event (not related by causality to treatment) used to describe causality to treatment; in that case, the terminology adverse reaction would be more appropriate.
The ICH brings together the regulatory authorities and pharmaceutical industry of Europe, Japan, and the United States (FDA) to discuss scientific and technical aspects of drug registration to promote safe, effective, high-quality drug development and registration. The definition of serious adverse reactions/events has been established by Guideline E2A in 1994. It originated from the ICH and is also followed by the FDA.  This definition helps to distinguish between serious and nonserious adverse reaction/events. Serious adverse reactions/events are any untoward medical occurrence that “results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, results in any other medically important condition.”  Based on this definition, the terminology used in the classifications of safety incidents identified by this literature review is not congruent with the ICH guidelines. For instance the term severe adverse events included hospitalization, permanent disability, and mortality, whereas a more appropriate terminology accurately describing this type of safety incident is serious adverse reaction.
The guideline E2B(R2) proposed by the ICH states that the database structure, design of paper form, control/quality assurances aspects, or technical security issues are not within its scope.  The E2B(R2) guideline was used as provided by the ICH and modified when required from drug interventions to manual procedures. The proposed extensive template of chiropractic safety incident reports is presented in Table 1. A common chiropractic template for collecting data could increase coherence as well as ease gathering and comparison of data collected in future chiropractic research. However, the exact template and the information to be collected could be further evaluated by researchers to produce continental (European, American, Australian, and others) or a common worldwide template. The identification of the operator may become a point of discussion because this is not currently performed with the Chiropractic Incident Reporting and Learning Systems.  The idea behind not identifying the operator is to promote trust and minimize the blame culture that may be associated with reporting safety incidents.  The identification or anonymity of the operator could be discussed and debated to promote reporting of safety incidents. The proposed template adapted from the ICH or another to be designed chiropractic template could greatly benefit the quality of the information collected on chiropractic safety incidents. In the absence of a common template of report and a centralized gathering database, the analysis of data and the comparison between studies could be hindered and may lead to confusion and/or inappropriate conclusions on the safety of chiropractic interventions in both pediatric and adult populations.
When reporting serious adverse reactions and events, it may be advisable to use an extensive template aimed at increasing understanding and promoting prevention of similar occurrences in the future. When reporting side effects and/or nonserious adverse events/reactions, the extensive template could be condensed into a shorter version that could include patient identification, chiropractor identification, information on the case, description of reaction or event (serious or not and highlighted or not), manual procedure, and case summary. The use of one, both, or a combination of extensive or short templates could be evaluated for feasibility and possible integration into existing or developing incident reporting systems such as the Chiropractic Incident Reporting and Learning Systems. 
Currently, safety incidents following pediatric manual procedures vary from 0.23% to 9%. [8-11] Four studies reporting primary data on pediatric safety incidents had retrospective designs and were subject to limitations including bias and external validity of results to the overall pediatric population. When observing the populations and the procedures performed (Table 2), it is observed that patient number, age, sex ratio, and number of treatment sessions were similar between studies, but differences were observed for cranial conditions and cranial treatments. Two studies reported cranial treatments, [9, 10] but cranial conditions were only reported in the study with the highest incidence.  It is plausible that the difference in frequency observed between rates of safety incidents may be associated with cranial conditions. In epidemiology, this is known as “selection bias,” “a distorted estimate of the effect that results from the way in which subjects are ascertained or selected for the study population, and includes factors such as differential surveillance, diagnosis, and referral of persons into the study”.  In this case, patients seen with cranial conditions and treated with cranial therapy may have distorted (increased) the rate of incident reports compared with studies where cranial conditions were not treated. This may indicate the importance of recording patient complaints and/or diagnoses when reporting safety incidents as certain conditions may be at higher risk of presenting adverse reactions or side effects during care.
Since 2003, serious adverse events and reactions have to be reported electronically using Medical Dictionary for Regulatory Activities (MedDRA) terminology. On its Web site, MedDRA is defined as “medical terminology used to classify adverse event information associated with the use of biopharmaceuticals and other medical products (e.g., medical devices and vaccines)”.  The medical profession and pharmaceutical industries in Europe, the United States, and Japan have been using MedDRA terminology and the E2B(R2) guideline to record complaints and safety incidents. Coding the entries of safety incidents into the standardized classification of MedDRA terms has allowed health authorities and the biopharmaceutical industry to more readily exchange and analyze data related to the safe use of medical products. 
Doctors of chiropractic are not regulated in the same manner as the pharmacological industry in reporting side effects and adverse reactions/events; however, using an internationally recognized system such as MedDRA may benefit the profession and lead to more accurate reports of safety incidents. In the future, MedDRA could be used considering its value in classifying conditions and in safety reports based on its international acceptance. Other possible options could include a system of classification of conditions tailor-made to pediatric chiropractic inspired from the pyramid structure of MedDRA in classifying conditions  or in designing a new system of classification all together. The advantages of adopting or constructing a worldwide or continental chiropractic classification are derived from a specific tailor-made classification. This could enable chiropractors to produce better quality of reports with increased coherence on terminology (conditions seen or safety incidents) and facilitate exchange of safety data. The aim of this methodology is to identify whether a condition is at higher risk for presenting side effects or adverse reactions in patients.
Another aspect to address in reporting pediatric chiropractic safety is the use of noncoherent terminology. The significant differences in terminology and definition between side effects, adverse reactions, and adverse events have not been considered by classification systems or studies providing primary data on pediatric safety in manual therapy. Differences in definitions and terminology may lead to misunderstanding as to the exact type of safety incident taking place and may lead to inexact conclusions in terms of safety of pediatric manual interventions. The terminology proposed by the WHO may be applicable to manual therapies by adapting the cause of treatment reaction from drug administration to the type of manual therapy performed. For instance, a patient breaking a leg outside of consultation time while in treatment for mechanical low-back pain could be classified as an adverse event because no direct link to the treatment can be established. An adverse reaction could occur in a patient in treatment for mechanical low-back pain reporting pain and tingling in a lower limb after spinal manipulative therapy because there is a possible link of causality to the treatment. A side effect could occur in a patient in treatment for mechanical low-back pain reporting soreness after treatment because this may be considered normal and of expected occurrence in patients after chiropractic care.
In some instances, it may be difficult to identify whether the safety incident is an adverse reaction or event. For instance, in the case study reporting a serious adverse reaction/event,  presence of extensive acute necrosis could be an adverse reaction to spinal manipulation (as indicated by the author) or an event associated with the presence of a particular pathology. The necrosis present could also be consistent with a spinal cord astrocytoma tumor grade 4 (glioblastoma multiforme) commonly presenting with necrosis and pathognomonic of palisading glioblastoma multiforme. It is important that, in the future, the terminology used is concordant between authors and that the methodology for reporting on safety incidents provides sufficient information to accurately describe the situation. Ultimately, the safety of manual therapies will be established on the occurrence of serious adverse reactions and the risk:benefit ratio.
The terminology used by the WHO and the ICH has been designed to address safety incidents related to the use of pharmaceutical interventions. Using identical terminology in manual therapy safety incidents may not be fully indicated. However, the use of standardized medical terminology with different chiropractic or manual therapy definitions and classifications may lead to misunderstanding and confusion in the future.
The difficulty currently faced by the chiropractic profession would be to differentiate between side effects and nonserious adverse reactions. Both classification systems currently available in pediatric manual therapy may be leading to confusion because of incorrect use of the terms serious and severe and incorrect use of either adverse events or reactions. The ICH and WHO classifications could help differentiate between the seriousness of adverse reactions (having implications on determining safety of intervention) and the severity of adverse reactions and side effects. Both current safety classifications [1, 13] could be used to better refine reports on the severity of side effects and nonserious adverse reactions/events. Recording, classifying, and differentiating between side effects and adverse reactions will help in promoting safer pediatric practice. By encouraging clinicians to report safety incidents in a constructive way, data could be gathered and analyzed. A list of normal side effects and out-of-the-norm adverse reactions could allow researchers to better search for and identify risk factors in the pediatric population. Academics would be able to educate both students and clinicians on such risks and clinicians to provide more accurate information to patients and parents along with aiming at decreasing risks of the welfare of patients. Therefore, it is important for evidence (ideally gathered prospectively) on the occurrence of side effects and adverse reactions to be recorded and published. After the establishment of a structured database for data collection, the profession will be in a better place to address and debate the differences between side effects and nonserious adverse reactions. These actions may help improve the safety of intervention by educating on risk factors and preventing the occurrence of serious adverse reactions.
Ultimately, the appropriate terminology on side effects, adverse reactions, and adverse events should be included in research publications, and terms should be used consistently. The methodology of report following pediatric safety incidents should aim at reaching the standards established by the ICH.
This article reviewed the literature in relation to use of terminology for safety incidents and their classification after spinal manipulation in pediatric patients. The search terms may have been too restrictive, leading to the possible omission of relevant articles. The gray literature was not searched, and only 1 electronic database was used as a search engine, which also may have omitted relevant articles. The inclusion and exclusion criteria also omitted articles on pediatric massage therapy and pediatric acupuncture. It is also possible that the modification of the ICH or the application of these guidelines may not be appropriate for chiropractic care and that other guidelines may be more conducive. Modifications were made by the author and were not validated.
Most of the articles identified by this literature review reporting on safety incidents following pediatric spinal manipulation or chiropractic manipulative therapy did not include terminology consistent with the standards established by the ICH and the WHO.
The safety terminology following pediatric manual therapy is not coherent
with the standards of the WHO and the ICH.
Reporting safety incidents based on the E2B(R2) guideline may improve
quality of data collection in chiropractic pediatric safety.
Safety of intervention will be based on serious adverse reactions and
the risk:benefit ratio of chiropractic treatment.
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